Differential Alteration in Vascular Structure of Resistance Arteries Isolated From the Cerebral and Mesenteric Vascular Beds of Transgenic [(mRen-2)27], Hypertensive Rats
Abstract In this study we examined the structural properties of cerebral and mesenteric resistance arteries isolated from normotensive, Sprague-Dawley (SD) rats (mean arterial pressure [MAP], 110±3 mm Hg) and hypertensive, transgenic (TG) rats (MAP, 167±4 mm Hg), which express the mouse Ren-2 renin gene. Vessels were set up in a pressure myograph, and ID and vascular wall thickness were determined at increasing intraluminal pressures. Arteries were subsequently pressurized to the MAP of the animal from which they were isolated and were fixed with glutaraldehyde before being embedded in araldite, sectioned, and examined histologically. The middle cerebral artery (MCA) isolated from SD rats and TG rats had similar media cross-sectional areas. There was no difference in MCA diameter at 10 mm Hg in vessels from TG rats compared with SD rats. However, at higher distending pressures, the diameter of the MCA from TG rats was significantly smaller than that of vessels from SD rats. This reduced ID at the higher pressures was a consequence of a decreased distensibility of the MCA from TG rats (as shown by a leftward shift of the stress-strain relationship in arteries from TG rats) and was not caused by an increase in wall thickness. First- and second-order mesenteric resistance arteries isolated from TG rats displayed an increased wall thickness and media content compared with vessels from SD rats. However, this alteration in mesenteric artery structure did not impinge on the ID of arteries from TG rats; there was no difference in the IDs of mesenteric resistance arteries between the two strains at any distending pressure. These observations show that there are distinct regional alterations in vascular structure in hypertensive TG rats expressing the mouse Ren-2 renin gene. Mesenteric resistance arteries isolated from TG rats display signs of vascular growth, although this structural alteration does not produce a reduction in the ID of these arteries per se. In contrast, cerebral arteries from TG rats do not show increased growth but have a reduced vascular distensibility, which results in a smaller ID compared with vessels from SD rats.
The introduction of the mouse Ren-2 gene into the rat genome has provided a transgenic animal that displays hypertension.1 The high blood pressure in these animals can be reduced by either short-term or long-term treatment with angiotensin receptor antagonists or ACE inhibitors.1 2 3 4 5 Although there is some debate about whether plasma renin levels are increased or decreased in TG rats (see Reference 66 for review), renal renin activity is suppressed in these animals.1 In contrast, there is a marked increase in the expression of extrarenal mouse renin, which has led to the suggestion that this model of hypertension is dependent on local tissue production of angiotensin II.1 2 7 8 Extrarenal mouse renin expression is greatest in the adrenal gland,1 with the resultant overproduction of steroid hormones being implicated in the hypertension in TG rats.9 However, it is also possible that the high blood pressure in TG rats is a consequence of activation of a localized vascular RAS. In support of this possibility, Ren-2 mRNA expression has been shown to be increased in the aorta and in the mesenteric vasculature of TG rats.7 Furthermore, angiotensin II production is markedly increased in the hindquarters vasculature and aorta from TG rats.7 10 The increased vascular production of localized angiotensin II could contribute to the hypertension in TG rats either by a direct10 or indirect10 11 vasoconstrictor action or by a trophic action on the structure of resistance arteries.12
We have recently shown that established hypertension in heterozygous (mRen-2)27 TG rats is characterized by a normal cardiac output and a generalized increase in vascular resistance,4 implicating an alteration in either the structure and/or function of small resistance arteries in maintaining the raised blood pressure in the established phase.13 In support of the possibility that structural alterations in resistance arteries may underlie the increased blood pressure in TG rats, it has been reported that there is a greater wall thickness in the aorta and, more importantly, in small coronary arteries and arterioles and renal arteries and arterioles isolated from TG rats compared with SD control rats.14 In addition, it has been reported that isolated mesenteric resistance arteries from TG rats have a smaller ID than vessels from normotensive rats, although in this study there was no evidence to suggest that vascular growth had occurred.15 In both of these studies, arteries were examined at a single distending pressure or degree of isometric stretch, thereby precluding determination of whether the reported differences in structure from TG rats were a consequence of an alteration in structure per se or due to an alteration in vascular mechanics (eg, artery distensibility) (see References 16 through 1816 17 18 ). In the present study, therefore, we examined the structural properties of mesenteric resistance arteries isolated from TG rats and SD rats, using the technique of pressure myography, to allow assessment of artery mechanics through a range of distending pressures, coupled with more detailed morphological characterization of these blood vessels. For comparison and to assess possible regional variations, we also examined the structural characteristics of cerebral resistance arteries isolated from TG rats and SD rats.
Animals were obtained from Dr J.J. Mullins (Centre for Genome Research, Edinburgh, UK) or were bred from animals supplied from that source. Male, heterozygous TG rats and age-matched, normotensive Sprague-Dawley rats (originally obtained from the Zentralinstitut für Versuchstierkunde, Hannover, Germany) were studied. The latter strain of rat was that used originally in the production of the TGR (mRen-2)27 strain.1 TG rats were bred in Nottingham by crossing male, homozygous TG rats with the control SD rats. The former were kept on long-term treatment with captopril (50 mg/L) added to the drinking water. We used untreated, heterozygous TG rats for our study in preference to homozygotes because the latter develop such severe hypertension that their survival rate without antihypertensive therapy is poor.1 Vessels isolated from TG rats (18±1 weeks old, 445±13 g, n=19) were compared with arteries isolated from age- and weight-matched SD control rats (19±1 weeks old, 435±11 g, n=14).
At least 48 hours before the in vitro analysis of vascular structure, rats were anesthetized (sodium methohexitone 60 mg/kg IP) and had an intra-arterial catheter implanted in the distal abdominal aorta (via the ventral caudal artery) and a venous catheter placed in the jugular vein. Catheters were tunneled subcutaneously and exteriorized at the back of the neck, from where they were led through a flexible spring. This spring was connected to a harness that was fitted to the rat and counterbalanced by a lever system that allowed the rat free movement when it was returned to its home cage. On the morning of experimentation, when animals were fully conscious and unrestrained, recordings were made of MAP over a 30-minute time period. Animals were subsequently anesthetized (sodium methohexitone, 4 to 10 mg/kg IV) and killed.
Protocol for Artery Selection
Care was taken to ensure that comparable arteries were examined from normotensive and hypertensive rats. Therefore, in experiments in which we examined mesenteric resistance artery structure, the mesentery was removed from each rat, whereupon the superior mesenteric artery was located and cleaned of connective tissue until the sixth branch leading to the gut wall was exposed. The second and third branches deriving from this branch were then used for study, as has been described previously.19 20 In experiments in which we examined the structural properties of cerebral vessels, the brain was removed and distal segments of the MCA before the major bifurcation of this vessel were dissected before further careful cleaning of adherent pia under a light microscope.
Analysis of Resistance Artery Structure
Resistance arteries were prepared for measurement of vascular diameter with a Halpern pressure-perfusion myograph.21 In brief, segments of the vessels were secured between two cannulas and tied with single strands (20-μm diameter) teased apart from a 1-cm length of surgical braided nylon suture. One cannula was closed and the other connected to a system containing PSS, which in turn was linked to a pressure-servo unit. The arteriograph was a 10-mL vessel chamber with an input and output channel to allow superfusion of PSS. The blood vessel was imaged with a videocamera and analyzed with an appropriate dimension analyzer (Living Systems Instrumentation), which was linked to a MAC-LAB data acquisition system in conjunction with a Macintosh computer (Performa 460).
The arteriograph in which the vessel was secured was connected to a 200-mL reservoir of PSS, which was bubbled with a 5% CO2/95% O2 gas mixture and circulated with a Masterflex pump (Cole-Parmer) at a rate of ≈10 mL/min. This ensured that the arteriograph volume was exchanged once per minute. Temperature was maintained at 37°C in the organ bath, and perfusate pH was continually monitored and held between 7.2 and 7.4.
For assessment of vascular structure, arterial segments were superfused with Ca2+-free PSS, and ID and wall thickness measurements were made through the pressure range of 10 to 170 mm Hg (in 40 mm Hg increments). At each pressure, along the length of the artery segment, eight measurements of arterial wall thickness and four measurements of ID were made and the results averaged. When pressurized, arterial segments underwent some longitudinal elongation (this effect was much larger for mesenteric than cerebral vessels, although there was no difference in the extent of elongation in arteries isolated from TG rats or SD rats; see “Results”). To compensate for any elongation, vessels were retracted with a micrometer to a length at which buckling was no longer apparent for each pressure. Once these measurements had been obtained, intraluminal pressure was set to the MAP of the rat from which the vessel had been isolated, and the vessel was exposed to a Ca2+-free PSS containing a 1.5% glutaraldehyde solution at 37°C for 30 minutes, which was then allowed to cool to room temperature over a further 60-minute period to fix the vessels. We have shown (see “Results” and Reference 1818 ) that this procedure minimizes shrinkage or contraction artifacts in mesenteric resistance arteries, although there was a small reduction in the measured ID of the MCA isolated from both SD rats and TG rats when compared by either the video system or histology (percent reduction in diameter, 11.9±4.9% for SD rats and 9.6±2.4% for TG rats). The cannulas to which arterial segments were attached were then broken and used to transport the vessel to a Petri dish, in which the segment was washed three times with Ca2+-free PSS and then stored overnight at 4°C. The following day, arteries were stained with 1% osmium tetroxide and dehydrated with acetone before being embedded in Araldite CY212 epoxy resin. Subsequently, sections 1 μm thick were cut and placed on glass microscope slides. Structural analysis of these sections was carried out with a morphometric grid, and luminal and media cross-sectional areas were determined. Because of the circular nature of the arterial cross section, values for lumen ID and average media thickness could subsequently be calculated.
The aortas from some animals were also removed, stained, and processed as outlined above (under zero-pressure conditions) to determine cross-sectional media content in a large conduit artery from SD rats and TG rats.
Calculation of Mechanical Characteristics
The mechanical characteristics of the resistance arteries were determined according to the method outlined by Baumbach and Heistad.16
Incremental distensibility was calculated from resistance artery ID (Di) and intraluminal pressure (IP): incremental distensibility=ΔDi/(Di×ΔIP)×100, where ΔDi is the change in resistance artery ID for each change of intraluminal pressure (ΔIP). Incremental distensibility therefore represents the percent change of arterial ID for each mm Hg change in intraluminal pressure.
Circumferential stress (ς) was calculated from IP, Di, and wall thickness (WT): ς=(IP×Di)/(2WT). IP was converted from mm Hg to N·m−2 (1 mm Hg=1.334×102 N·m−2). Since wall thickness varied markedly with alterations in intraluminal pressure, particularly for mesenteric arteries (see Fig 2⇓), the wall thickness measured at each individual intraluminal pressure was used for these calculations.
Circumferential strain (ε) was calculated from: ε=(Di−Do)/Do, where Do is the original diameter. ID measured at 10 mm Hg was used for the original diameter in the calculation of circumferential strain, because it is difficult to accurately determine the ID of resistance arteries at pressures lower than this.16
The stress-strain data for individual vessels were fitted to an exponential curve (y=aebx) to obtain the slope of the tangential elastic modulus versus stress16 17 from the equation ςi=ςorigeβε, where ςorig is the stress at the original diameter (in this case the diameter at 10 mm Hg) and β is the slope of tangential elastic modulus versus stress.
Where appropriate, results are shown in the text and figures as mean±SEM (number of animals or vessels). Differences between means were considered significant if P<.05 by Student’s paired or unpaired t test.
Drugs and Solutions
The following drugs and chemicals were used: osmium tetroxide (Johnson Matthey), Araldite CY212 epoxy resin (TAAB Laboratories), and glutaraldehyde (TAAB Laboratories). The composition of the calcium-free PSS was as follows (in mmol/L): NaCl 119, NaHCO3 24, KCl 4.7, KH2PO4 1.17, MgSO4·7H2O 1.17, Na2EDTA 0.023, glucose 5.5, and EGTA 0.5.
Mean Arterial Pressure
We used 14 SD rats and 19 TG rats in the present study. TG rats had a MAP of 167±4 mm Hg (n=19) compared with 110±3 mm Hg (n=14) in SD rats.
There was no difference in the IDs of the MCA isolated from TG rats or SD rats at 10 mm Hg (Fig 1⇓). However, the MCA from TG rats had a smaller ID than the MCA isolated from SD rats at pressures of ≥30 mm Hg (Fig 1⇓). This observation was confirmed by histological determination of MCA morphology when arteries were fixed at high pressures (Table⇓).
The wall thickness of cerebral arteries decreased with increasing intraluminal pressures (Fig 2⇓). This is a consequence of both the increase in ID and the elongation of resistance arteries that occurs on pressurization. The extent of variation in length in the MCA with increasing pressure was relatively small. In addition, the degree of elongation did not differ in arteries isolated from either SD rats or TG rats (in a subset of rats, the increase in length on pressurization from 10 mm Hg to 170 mm Hg was 13.3±1.9% in the MCA from SD rats and 15.0±2.4% in the MCA from TG rats [n=6]). At comparable intraluminal pressures, there was a slightly greater wall thickness of the MCA isolated from TG rats compared with vessels isolated from SD rats throughout the pressure range when measured on the video screen (Fig 2⇓). However, there was no significant difference in either wall thickness or media content in the MCA isolated from either strain when fixed at the MAP of the rats from which they were isolated and examined in detail histologically (Table⇑).
In the MCA isolated from TG rats, there was a reduced incremental distensibility compared with the MCA isolated from SD rats (Fig 3a⇓), and the stress-strain curve in hypertensive rats was shifted to the left of that for the MCA from normotensive rats (Fig 3b⇓), thus demonstrating that arterial distensibility was decreased over the range of the pressure-diameter curve. This was confirmed by the slope of tangential elastic modulus versus stress (β), which was significantly greater in the MCA isolated from TG rats than from SD rats (13.4±0.8 versus 9.2±1.0, P<.05, Student’s t test).
Mesenteric Resistance Artery Structure
There was no difference in ID of second-order mesenteric resistance arteries isolated from either SD rats or TG rats regardless of the distending pressure and when viewed with either the video-dimension analyzer (Fig 4a⇓) or the more detailed histological examination (Table⇑). Similarly, there was no difference in the ID of third-order mesenteric resistance arteries isolated from either strain when examined with either methodology (Fig 4b⇓, Table⇑).
At comparable intraluminal pressures, there was a greater wall thickness in second- and third-order mesenteric resistance arteries isolated from TG rats compared with vessels isolated from SD rats, which was significant at most pressures and particularly evident at lower pressures (Fig 5⇓). More detailed histological examination of these vessels demonstrated a greater media content of the arteries isolated from TG rats and an increased media-to-lumen ratio of vessels from the hypertensive rats when stained at the MAP of the rat from which they were isolated (Table⇑).
Mesenteric resistance arteries underwent elongation when pressurized. This effect was more prominent than the elongation observed in the cerebral arteries, but the extent of variation in length of mesenteric resistance arteries with increasing pressure did not differ in arteries isolated from either SD rats or TG rats (in a subgroup of rats, second-order vessels increased in length by 96.0±14.0% and 92.0±7.0% on pressurization from 10 to 170 mm Hg in arteries from TG rats and SD rats, respectively [n=3]). Furthermore, there was no significant difference in incremental distensibility in either second- or third-order arteries isolated from normotensive or hypertensive rats (Figs 6a⇓ and 7a⇓), and the stress-strain curves for mesenteric arteries from SD rats and TG rats overlapped (Figs 6b⇓ and 7b⇓). The slope of tangential elastic modulus versus stress (β) for second-order mesenteric vessels from TG rats was 5.0±0.4 compared with 5.0±0.6 for vessels from SD rats, whereas for third-order arteries, the values for β were 4.7±0.3 and 4.5±0.2, respectively. Thus, in contrast to the MCA and despite the difference in media content, there was no evidence to suggest that mesenteric resistance arteries isolated from TG rats were any more or less distensible than vessels isolated from SD rats.
The aortas isolated from TG rats had a greater media content than the aortas isolated from SD rats (Table⇑).
The main findings of the present study are that in TG rats expressing the mouse Ren-2 renin gene, (1) there are regionally selective reductions in the ID of resistance arteries due to local modifications in vessel distensibility: cerebral but not mesenteric resistance arteries isolated from TG rats are less distensible than vessels isolated from SD rats; and (2) there are regionally selective alterations in vascular growth in resistance arteries isolated from TG rats and SD rats; mesenteric but not cerebral resistance arteries isolated from TG rats have an increased media content compared with vessels isolated from SD rats.
In recent years, increased attention has focused on the potential role for alterations in the structure of small arteries in contributing to the increased resistance observed in the established phase of human essential hypertension and in experimental animal models of hypertension. Data from many studies have indicated that the ID of arteries from hypertensive animals is smaller than that of equivalent vessels from normotensive controls (see References 12, 13, and 2212 13 22 through 27 for reviews). This has been suggested to be a consequence of vascular growth, stimulated by high blood pressure per se26 or by humoral agents,12 or to be due to a mechanism whereby vascular diameter is reduced, not by an increase in media thickness (hypertrophy) but rather by a remodeling of existing wall material.22 However, in the majority of studies that have examined vascular structure, measurements of resistance artery morphology were carried out at a single distending pressure or degree of isometric stretch, which does not allow discrimination between remodeling or alterations in vascular distensibility. In the present study, we have shown that the MCA isolated from TG rats has a smaller ID than the equivalent artery isolated from SD rats at intraluminal pressures >10 mm Hg, a feature that could contribute to the increased vascular resistance observed in TG rats.4 However, the reduction in ID of the MCA was not due to either vascular hypertrophy or remodeling but rather to a reduced distensibility of arteries isolated from TG rats. This is shown clearly by the similarity in the ID of MCAs isolated from either TG rats or SD rats at minimal distending pressures compared with the reduced ID of arteries from TG rats at higher pressures and by the leftward shift in the stress-strain relationship in the MCA isolated from TG rats compared with vessels from SD rats (Fig 3b⇑). Similar observations have previously been made for large branches of the posterior cerebral artery in stroke-prone SHRs18 and for the basilar artery in SHRs.27 This may be a feature common only to larger cerebral arteries, since smaller branches of the posterior cerebral artery from stroke-prone SHRs display a paradoxical increase in distensibility, despite signs of hypertrophy and a reduced ID.18
We have previously discussed the difficulties involved in examining resistance artery structure.19 28 It is particularly problematic to determine the appropriate intraluminal pressure each arterial branch would be exposed to in the conscious rat to set the appropriate pressure in vitro. Therefore, most studies have examined resistance arteries isolated from either normotensive or hypertensive animals either at the same distending pressure (or tension) or at different pressures proportional to the MAP of the particular animal from which vessels were isolated.15 19 In the absence of data for microvascular pressures in regional vascular beds in conscious SD and TG rats, we have maximized our observations by comparing arteries isolated from either strain of rat by two approaches. Initially, we examined vessels through a wide range of pressures using the video-dimension analysis system before finally staining vessels for more detailed histological examination at the MAP of the animal from which vessels were isolated. These two methods gave qualitatively similar results for the structure of cerebral resistance arteries. At high pressures, the ID of the MCA isolated from TG rats was shown to be smaller than that from SD rats by either method. On first appearance, the measurement of wall thickness using either method appears to differ. There was a significant, albeit small, difference in wall thickness in the MCA isolated from TG rats compared with SD rats when measured with the video system. In contrast, there was no difference in wall thickness of the MCA from either strain by the histological method. However, the measurements using the video system were made at the same pressure, whereas the histological measurements were made at different pressures. When we compared wall thickness on the video system at pressures approximately equal to the MAP of SD and TG rats, respectively, the small difference in wall thickness disappeared (SD rats, 14.2±0.4 versus TG rats, 15.4±0.5 μm, P>.05). More importantly, we showed that the MCA from SD rats and TG rats had a similar media content, indicating that no vascular growth had occurred in these cerebral resistance arteries and that the reduced ID of these vessels at intraluminal pressures >10 mm Hg was not due to vascular hypertrophy or hyperplasia.
Unlike the observations in the MCA, the ID of second- and third-order mesenteric resistance arteries isolated from TG rats was not different from vessels isolated from SD rats. Furthermore, the stress-strain relationships for mesenteric resistance arteries overlapped, indicating that there was no alteration in the distensibility of these vessels between the two strains, even though mesenteric resistance arteries isolated from TG rats had a greater media content than arteries isolated from SD rats, as shown by the detailed histological assessment of these vessels. Similar, regionally selective alterations in vascular distensibility have also been seen in arteries isolated from SHRs compared with vessels isolated from WKY control rats, ie, cerebral but not mesenteric resistance arteries isolated from SHRs were less distensible than those from WKY rats, although vessels in this latter study were examined isometrically.29 These authors suggested that this regionally selective alteration in vascular distensibility was a consequence of an increased collagen content in cerebral arteries from SHRs and that it could act to modify the autoregulatory capability of cerebral blood vessels29 in hypertensive animals and hence oppose the potentially damaging effects of excesses in pressure. Whether the reduced distensibility of cerebral arteries from TG rats is consequent to an increase in collagen content remains to be determined.
Although an increased wall thickness of mesenteric resistance arteries isolated from TG rats was evident by both histological and video methods, this observation was less apparent with the latter technique. Indeed, there were some points on the pressure–wall thickness curve at which there was no significant difference in wall thickness of arteries isolated between the two strains. Taken in isolation, the measurement of wall thickness at these points could be taken as evidence for a lack of vascular growth. This observation emphasizes the importance of carrying out detailed histology to determine media content as the indicator of vascular growth rather than relying on the shadow produced by transillumination of resistance arteries as the sole measure of wall thickness (and hence of growth), since video-dimension analysis does not allow discrimination between adventitia and media content and is potentially susceptible to optical errors.
Our observations in mesenteric resistance arteries isolated from TG rats contrast with a previous report that suggested that mesenteric vessels had a reduced ID compared with vessels from SD rats.15 There are a number of possible explanations for the disparity between these studies. Perhaps the most likely is the method used for examining resistance artery structure. We used the pressure myograph system in contrast to the isometric myograph technique used by Thybo et al.15 We have recently outlined the benefits of the more physiological pressure myograph technique.19 28 Alternatively, the results may reflect age-related alterations in vascular structure, since we used older rats (19 weeks versus 13 weeks) than Thybo et al. Other alternatives are that our observations reflect structural differences related to sex differences,6 differences in the control strain of SD rat used,6 or perhaps more interestingly, a difference between homozygous and heterozygous TG rats, although Thybo et al did not describe in detail the rats used in their study.
Another difference between the results of our study and those of Thybo et al was that we have demonstrated an increase in media content, wall thickness, and wall-to-lumen ratio in mesenteric resistance arteries and in the aorta isolated from TG rats, indicative of a generalized increase in vascular growth in peripheral vascular beds in this hypertensive model, whereas they had no evidence for vascular growth in mesenteric vessels. Again, this discrepancy may relate to the method used for examining resistance artery structure.19 29 However, our observations in mesenteric resistance arteries compare well with the increased wall thickness reported in perfusion-fixed renal and coronary arteries and arterioles isolated from TG rats compared with vessels isolated from SD rats.14 Bachmann et al14 also demonstrated an increased media thickness in aorta isolated from TG rats. In addition, it has been reported that there is an increase in thymidine uptake in cultured vascular smooth muscle cells isolated from TG rats compared with SD rats.30 We have recently shown that increased pressure per se is an insufficient stimulus to promote vascular growth19 ; therefore, a potential cause of the increase in vascular growth could be the trophic actions of locally produced angiotensin II.31 Alternatively, the increased vascular growth could be a consequence of a trophic action of other compounds produced locally in the microvasculature, such as endothelin,32 which contributes to the maintained phase of the hypertension in TG rats.4 Indeed, the potential importance for a mechanism other than angiotensin II in mediating vascular growth is emphasized by the observation that the increased thymidine uptake in cultured vascular smooth muscle cells from TG rats is not blocked by either ACE inhibitors or angiotensin receptor blockers.30 As mentioned earlier, the contribution of vascular hypertrophy to the increased vascular resistance in TG rats per se is limited; however, the increased media content may contribute to an enhanced sensitivity of arterial vessels to vasoconstrictors. The reasons for a lack of vascular growth in cerebral resistance arteries is unknown; it is possible that the receptor subtypes responsible for the trophic actions of the above trophic agents are not present on cerebral blood vessels or that those vessels lack the mechanisms to produce appropriate and necessary growth factors.
In summary, the TG rat represents a model of hypertension that displays regionally selective increases in vascular growth, although the increased media content in mesenteric vessels isolated from TG rats does not impose a significant reduction in the ID of small resistance arteries per se. The increased vascular smooth muscle content in these vessels could lead to an enhanced sensitivity of mesenteric resistance arteries to vasoconstrictors. In addition, there is a regionally selective reduction in vascular distensibility. There is no alteration in distensibility of mesenteric resistance arteries from normotensive or hypertensive rats. In contrast, the MCAs isolated from TG rats have a smaller ID than the MCAs isolated from SD rats due to a decrease in distensibility.
Selected Abbreviations and Acronyms
|MAP||=||mean arterial blood pressure|
|MCA||=||middle cerebral artery|
|PSS||=||physiological salt solution|
|SHR||=||spontaneously hypertensive rat|
The authors thank Professor Terence Bennett for his advice and constructive comments and Dr John J. Mullins for providing breeding pairs of SD and TG rats.
Reprint requests to William R. Dunn, Department of Physiology and Pharmacology, Queen’s Medical Centre, Medical School, University of Nottingham, Clifton Blvd, Nottingham, NG7 2 UH, UK.
- Received August 23, 1996.
- Revision received October 1, 1996.
- Accepted November 12, 1996.
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