(Hypertension. 1996;28:779-784.)
© 1996 American Heart Association, Inc.
Articles |
Disproportional Arterial Hypertrophy in Hypertensive mRen-2 Transgenic Rats
the Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of Limburg (the Netherlands) (H.A.J.S.-B., H. van E., G.F., J.G.R. De M.), and INSERM Unite 141, Hopital Lariboisiere, Paris, France (Y.Q., B.I.L.).
Correspondence to Harry A.J. Struijker-Boudier, Department of Pharmacology, University of Limburg, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail h.struijkerboudier@farmaco.rulimburg.nl.
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Abstract |
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In the present study, we investigated the role of enhanced vascular renin-angiotensin activity in vascular hypertrophy. We used transgenic (mRen-2)27 (renin TGR) rats, spontaneously hypertensive rats (SHR), and their respective normotensive control rats to study in situ pressure-diameter relationships in second-generation mesenteric arterial branches (in vivo diameter, 400 to 500 µm) over a pressure range of 0 to 200 mm Hg. We studied pressure-diameter curves under both control (Tyrode's solution) and fully relaxed (Tyrode's solution containing 100 mg/L potassium cyanide) conditions. From these curves, we determined mechanical properties at operating blood pressure. In both hypertensive strains, mesenteric arterial media cross-sectional area was increased, with a significantly (P<.05) stronger degree of hypertrophy in renin TGR rats. Arterial distensibility of relaxed vessels was decreased to an equal degree in both hypertensive strains. Under control conditions, distensibility was higher in SHR than in renin TGR rats but still significantly reduced compared with distensibility in normotensive rats. Wall tension was increased to an equal degree in both hypertensive strains, whereas circumferential wall stress was normal in SHR but significantly (P<.05) reduced in renin TGR rats. These results indicate that whereas vascular hypertrophy in SHR causes adaptive normalization of arterial wall stress, enhanced vascular renin-angiotensin activity causes vascular hypertrophy in excess of the hypertrophy associated with pressure elevation alone.
Key Words: renin-angiotensin system • hypertension, genetic • rats, transgenic • rats, inbred SHR • arteries • hypertrophy • compliance
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Introduction |
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The renin-angiotensin system plays a major role in the control of vascular function. At the level of the microcirculation and small arteries, Ang II influences resistance to flow, whereas in large arteries, it may affect the conduit and buffering function of the arterial system. The mechanisms underlying these vascular effects involve (1) acute, vascular smooth muscle cell–mediated contractile actions of Ang II; (2) direct, long-term structural effects on the vessel wall; and (3) long-term structural and functional adaptive changes secondary to the increased arterial pressure.1 2 3 4 5
The recent introduction of renin TGR rats has provided a powerful tool for study of the potential role of the renin-angiotensin system in the control of vascular function.6 7 In renin TGR rats, an additional mouse Ren-2 gene has been integrated into the genome, resulting in a marked increase in blood pressure.6 7 In this transgenic strain, plasma renin activity is low, but its local expression and activity in various tissues, including the vasculature, is high.7 8 9 10 Treatment of renin TGR rats with angiotensin-converting enzyme inhibitors or type 1 angiotensin receptor antagonists causes a normalization of blood pressure, indicating that the hypertension depends largely on Ang II.11 12
In the present study, we determined the extent of arterial structural changes in renin TGR rats and evaluated whether these merely represent an adaptation to elevated wall tension. For comparison, we included SHR in our analysis. In this genetic model of hypertension, both circulating and local renin-angiotensin activities are normal or even reduced.13 We investigated vascular structure and function using an in situ model for studying mesenteric arteries.14 15
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Methods |
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Animals
Renin TGR rats were obtained from the Center for Genomic Research (Edinburgh, Scotland; Dr J. Mullins). SDH rats were purchased from the Zentralinstitut fur Versuchstierkunde (Hannover, Germany). SHR and WKY were obtained from breeding colonies maintained at the Central Animal Facilities of the University of Limburg. Rats were housed individually and had free access to food and water. At the time of the experiments, rats were 14 to 16 weeks old. All experiments were approved by the Animal Care Committee of the University of Limburg.
Experimental Model
The experimental setup of the in situ mesenteric artery has been described previously in detail.14 15 In brief, with rats under sodium pentobarbital anesthesia (60 mg/kg IP), a catheter was introduced into the abdominal aorta via the left femoral artery for recording of arterial blood pressure. A median laparotomy was then performed, and the most distal loop of the small intestine was exteriorized. It was exposed on an optical glass piece and irrigated by a buffered Tyrode's solution (pH 7.4) at 38°C. A short segment (approximately 3 mm) of a second-generation mesenteric arterial branch (diameter, 400 to 500 µm) was exposed and gently dissected under a binocular lens (Wild M5A). These vessels are one or two generations upstream of the mesenteric resistance-sized arteries usually used in in vitro myograph setups.5 Video images of the vessel were recorded via a camera (CCD, Sony) mounted on the binocular lens. The optical and recording systems had been previously calibrated. Final magnification was x100. All arterial branches located downstream of the observed segment of artery, except one, were ligated. A polyethylene catheter (external diameter, 0.25 mm; internal diameter, 0.10 mm) was introduced into this branch for local mesenteric arterial pressure measurements with a flow-through pressure transducer (Micro Switch 150 PC). The same catheter was connected via a three-way tap to a manometer with adjustable pressure levels. After a removable microclamp was put proximally on the observed segment, the artery was exposed to different pressures, and diameter changes were observed. External diameters were measured with an image shearing monitor (model 908, PTM). The artery was exposed to pressure steps of 25 mm Hg from 0 to 200 mm Hg at 4-minute intervals. Video recordings of the last 30 seconds of each pressure step were used for diameter measurement.
Study Protocol
After surgical procedures, aortic and distal mesenteric arterial pressures were recorded for 20 minutes. Mean pressures were obtained by high-frequency filtering of the pressure signal on the recorder. In a separate series of experiments in five SHR and five renin TGR rats, we compared mean aortic pressure with rats in the conscious state and after pentobarbital anesthesia and laparotomy. The influence of pentobarbital anesthesia and laparotomy on mean aortic pressure was comparable (24% to 29% reduction) for the two hypertensive strains. The mean mesenteric arterial pressure in the anesthetized rats was used in the subsequent analyses as the operating pressure for the artery studied. Next, measurements of mesenteric arterial pressure-diameter relationships were made during superfusion with normal Tyrode's solution (control conditions). The mesenteric artery then was incubated for 30 minutes at a transmural pressure of 75 mm Hg with Tyrode's solution containing 100 mg/L potassium cyanide. This incubation is sufficient to poison arterial smooth muscle and abolish smooth muscle tone.16
At the end of each experiment, the mesenteric artery was flushed and filled with a fixative of 4% formaldehyde in phosphate-buffered saline. The vessel was maintained for 20 minutes under these conditions at its individual mesenteric arterial pressure. The vessel was then excised and processed for measurement of medial cross-sectional area by semiautomated morphometry after staining of cross sections with Lawson's solution.17
Data Calculation
On the basis of the measured value of medial cross-sectional area (CSA, micrometers squared) and external diameter (De, micrometers) over the pressure range of 0 to 200 mm Hg, the following variables were calculated: medial thickness (h, micrometers): h=CSA/(
De), on the basis of the assumption of a noncompressible arterial wall; internal diameter (Di, micrometers): Di=De-2h; lumen volume (Vi, microliters) per unit length: Vi=Di2/4; compliance (C, microliters per millimeters of mercury) per unit length: C=
V/P, where V is the volume change induced per pressure change (P) of 25 mm Hg; distensibility (D, per millimeters of mercury) per unit length: D=C/Vi; wall tension (WT, newtons per meter): WT=PxDi/2 on the basis of Laplace's law; and circumferential wall stress (WS, kilopascals): WS=WT/h.
The variables were measured for each pressure applied. In addition, their values were determined at the actually measured mean mesenteric arterial pressure for each rat by interpolation from the whole pressure curves.
Statistical Analysis
Results are expressed as mean±SE. Statistical significance was evaluated by two-tailed Student's t test or ANOVA followed by Newman-Keuls test.18 Results were considered significantly different at a value of P<.05.
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Results |
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Table 1
presents basic results. Total body weight was lower in the two hypertensive rat strains. The difference reached statistical significance in SHR versus WKY (P<.05). In both hypertensive strains, mean aortic pressures and mean mesenteric arterial pressures were significantly (P<.01) higher than in normotensive strains. The degree of pressure elevation was comparable for the two hypertensive strains. Mean mesenteric arterial pressures were 10 to 24 mm Hg lower than mean aortic pressures. The in situ measured external diameters of the mesenteric artery at respective operating pressures did not differ significantly between the hypertensive and normotensive strains. Cross-sectional area of the mesenteric arteries was increased by 121% (P<.01) in renin TGR rats and 46% (P<.05) in SHR compared with their corresponding normotensive controls. The increase in cross-sectional area was significantly (P<.05) larger in renin TGR rats than SHR.
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Fig 1 shows the pressure-diameter relationships for the four rat strains under normal and passive smooth muscle conditions. At low pressures, the vessels exhibited larger changes in diameter with each step increase in pressure, whereas at high pressures, diameter changes per pressure increase were minor. At operating pressures, external diameters of the mesenteric artery did not differ significantly between the hypertensive and normotensive rat strains (Table
s 2 and 3).
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, left), SDH rats (
, left), SHR (
Pressure-volume curves allow the determination of compliance and distensibility changes over the pressure range investigated. Compliance and distensibility were highest in the pressure range of 25 to 75 mm Hg. In this range, compliance and distensibility were always significantly lower in the hypertensive strains than the normotensive controls. At equal pressures of 100 mm Hg, compliance and distensibility did not differ significantly in renin TGR versus SDH rats or SHR versus WKY. However, when compared at operating pressures, compliance and distensibility were again significantly lower in both hypertensive rat strains than in their normotensive controls under basal and passive smooth muscle conditions (Tables 2 and 3). In fully relaxed vessels, vascular distensibility was lowered to an equal degree in both hypertensive strains. Under basal conditions, distensibility was slightly higher in SHR (3.2±0.2x10-3 mm Hg-1) than in renin TGR rats (2.2±0.2x10-3 mm Hg-1). In a two-way ANOVA, this difference did not reach statistical significance.
Fig 2 presents the wall tension calculated in the four rat strains under the different experimental conditions. The curves are very similar for the various strains and different conditions. When calculated at the operating pressures, wall tension was significantly larger in both hypertensive strains than in their normotensive controls under both basal and passive conditions (Tables 2 and 3).
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The pressure–circumferential wall stress curves (Fig 3) were similar in the two experimental conditions. In each case, the stress curves were steeper for the normotensive controls than for renin TGR rats or SHR (P<.05 in each case). The differences were larger for renin TGR versus SDH rats than for SHR versus WKY (Fig 3). At operating pressures, the mesenteric arterial wall stress was significantly lower in renin TGR than in SDH rats (Table 2), whereas there were no significant differences in SHR and WKY (Table 3).
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Discussion |
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This study shows that renin TGR rats have an increased mesenteric arterial medial cross-sectional area. This increase is larger than that noted in SHR. The increased mesenteric arterial medial cross-sectional area is associated with a decreased arterial distensibility and increased wall tension at operating pressures. In SHR, circumferential wall stress is normal, whereas in renin TGR rats, mesenteric arterial hypertrophy is associated with a significant reduction in wall stress.
The considerable increase in mesenteric arterial medial cross-sectional area is well in line with previously reported vascular growth activity of Ang II.19 20 21 22 Vascular smooth muscle cell cultures19 20 as well as in vivo large and small arteries exhibit a growth response after chronic administration of Ang II, even at subpressor doses.21 22 On the microcirculatory level, Ang II–induced vascular growth is expressed as an angiogenic effect, probably most strongly at the capillary and venular levels.23 24 Our data show that at least at the level of intermediate-sized mesenteric arteries (approximate external diameter, 400 to 500 µm), enhanced local renin-angiotensin activity is associated with medial hypertrophy. Similar conclusions were reached for aorta and renal and coronary arteries in renin TGR rats9 and angiotensin-converting enzyme gene–transfected rat carotid arteries.25 In femoral arterial vascular smooth muscle cell cultures from renin TGR rats and normotensive Sprague-Dawley rats, cells from renin TGR rats show a higher rate of DNA synthesis than those from Sprague-Dawley rats.26 However, our data are at variance with a study27 in which the morphology of 200- to 250-µm-diameter mesenteric arteries from 13-week-old renin TGR and Sprague-Dawley rats were compared. In that study, an increased media-lumen ratio was found without a significant increase in medial area. The authors interpreted their data as a reorganization of the existing vascular smooth muscle around a smaller lumen. This type of vascular remodeling was suggested to reflect an adaptation to the elevated pressure rather than a primary growth response to the elevated vascular renin-angiotensin activity. A possible explanation for these apparently discrepant observations is the difference in size and functional role of the arteries investigated. The arterial segment we studied plays a less important role in resistance than the 200- to 250-µm vessels studied by Thybo et al,27 as was recently shown by direct pressure measurements.28 In a series of recent studies, we also failed to observe a vascular growth response in terms of angiogenesis on the small arteriolar level of renin TGR rats (H.A.J. Struijker-Boudier et al, unpublished observations, 1996). A heterogeneous growth response of various segments of the mesenteric arterial tree is not a unique feature of renin TGR rats. In previous studies, comparable differences were reported for small and large mesenteric arterial branches in 16-week-old SHR compared with WKY.29 The heterogeneous growth response of various segments of the arterial tree in hypertension may be due to the differential presence of various smooth muscle cell types, some of which are influenced by hemodynamic changes, whereas others are not.30 Taken together, these data may imply that distal from a certain level within the arterial and arteriolar trees, a potential vascular growth effect of Ang II is overridden by another factor, causing remodeling at the small arterial level and rarefaction at the arteriolar level. Recent experimental data and computer simulations suggest that elevated blood pressure and related increases in wall tension may be this factor.31 This hypothesis implies three basically different responses to pressure elevation in the arterial tree: hypertrophy of large arteries, remodeling of small arteries, and rarefaction of precapillary arterioles.
The present study shows that the degree of mesenteric arterial medial hypertrophy in renin TGR rats is stronger than in SHR. In fact, in SHR the degree of medial hypertrophy compensates exactly for the rise in arterial pressure and, according to Laplace's law, increase in wall tension. In this respect, mesenteric arterial hypertrophy in SHR is a good example of "adaptive" hypertrophy aimed at the maintenance of normal circumferential wall stress.32 In renin TGR rats, the growth response seems stronger than required for this type of adaptation. Indeed, wall stress is reduced to a level significantly below that in SHR or normotensive rats. The maintenance of a constant wall stress is believed to serve the functional integrity of the vessel wall.32 Research on the functional consequences of abnormal wall stresses have thus far focused on situations of increased wall stress, as occur in arterial aneurysms.33 Renin TGR rats might provide a useful model for study of the consequences of lowered arterial wall stress.
The hypothesis that renin TGR rats exhibit arterial hypertrophy in excess of that required to compensate for elevated transmural pressure obviously depends on the pressure that the vessels experience under normal conditions. Our experiments show that in the anesthetized state, aortic and mesenteric arterial pressures do not differ significantly between renin TGR rats and SHR. Furthermore, the influence of anesthesia and laparotomy on arterial pressure was equal for renin TGR rats and SHR. However, we cannot exclude the fact that interstrain differences exist with respect to the pressure load the two strains have experienced preceding the measurements. This load is determined by the duration of hypertension and the 24-hour variability in blood pressure.34 Furthermore, a major role for pulse pressure rather than mean pressure cannot be excluded.35
Unfortunately, the technology is not yet available to be able to approach these important issues in small muscular arteries of intact, conscious animals. Tail-cuff measurements of systolic pressures in the tail arteries suggest that renin TGR rats and SHR have comparable patterns of hypertension development, with the most significant rise in pressure occurring between 4 and 8 weeks after birth.6 We have recently described a noninvasive ultrasound technique that may allow investigation of the interrelationship between neurohormonal mechanisms, hemodynamic factors, arterial wall mechanics, and arterial wall structure at the level of large elastic arteries in rats.36 This technique may be suitable for future experiments to address the contribution of pressure load over a prolonged period of time.
Mechanical consequences of increased vessel wall mass may include a reduction of vascular distensibility. When comparing at the operating pressures, we observed reductions in mesenteric arterial distensibility in both renin TGR rats and SHR in relation to their corresponding controls. However, in the higher pressure range (100 mm Hg and above), the decreased compliance and distensibility in hypertensive rats seem primarily caused by the higher operating pressure. Hayoz et al37 reached a similar conclusion in a study in which they compared carotid arterial mechanics of SHR versus WKY by means of echo-tracking techniques. These authors even found an increased carotid arterial distensibility in SHR when compared under isobaric conditions with WKY. The reduced compliance and distensibility of the SHR aorta, on the other hand, seem at least partially independent of pressure.38 Again, the nature of the vascular change in hypertension seems to depend on the location of the vascular segment.
In conclusion, this study demonstrates a mesenteric arterial medial hypertrophy in renin TGR rats that is larger than that in SHR with a comparable rise in arterial pressure. The medial hypertrophy of mesenteric arteries from renin TGR rats exceeds the level needed for maintenance of normal wall stress. At the level of the mesenteric artery, enhanced renin-angiotensin activity is thus causing a vascular growth response that is at least partly independent of pressure.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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These studies were supported by a grant from the European Community in the BIOMED-1 program. The authors gratefully acknowledge the support of Dr John Mullins in obtaining renin TGR. They thank Els Geurts and Mia Hogenboom for secretarial assistance.
Received October 30, 1995;
first decision November 21, 1995; first decision June 28, 1996;
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References |
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1. Brown AJ, Casals-Stenzel J, Gofford S, Lever AF, Morton JJ. Comparison of the fast and slow pressor effects of angiotensin II in the conscious rat. Am J Physiol. 1981;241:H381-H388.
2. Levy BI, Michel JB, Salzmann JL, Azizi M, Poitevin P, Safar ME, Camilleri JP. Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension. Circ Res. 1988;77:947-954.
3.
Levy BI, Benessiano J, Poitevin P, Safar ME. Endothelium-dependent mechanical properties of the carotid artery in WKY and SHR. Circ Res. 1990;66:321-328.
4.
Dzau VJ, Safar ME. Large conduit arteries in hypertension: role of the vascular renin-angiotensin system. Circulation. 1988;77:947-954.
5. Mulvany MJ. Resistance vessel structure in hypertension: growth or remodeling? J Cardiovasc Pharmacol. 1993;22(suppl 5):S44-S47.
6. Mullins JJ, Peters J, Ganten D. Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature. 1990;244:541-544.
7. Paul M, Wagner J. Transgenic rats: new experimental models for the study of candidate genes in hypertension research. Annu Rev Physiol. 1994;56:811-829.[Medline] [Order article via Infotrieve]
8.
Hilgers KF, Peters J, Veelken R, Sommer M, Rupprecht G, Ganten D, Luft FC, Mann JFE. Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene. Hypertension. 1992;19:687-691.
9. Bachmann S, Peters J, Engler E, Ganten D, Mullins J. Transgenic rats carrying the mouse renin gene: morphological characterization of a low-renin hypertension model. Kidney Int. 1992;41:24-36.[Medline] [Order article via Infotrieve]
10.
Zhao Y, Bader M, Kreutz R, Fernandez-Alfonso M, Zimmermann F, Ganten U, Metzger R, Ganten D, Mullins JJ, Peters J. Ontogenetic regulation of mouse Ren-2d renin gene in transgenic hypertensive rats, TGR(mREN2)27. Am J Physiol. 1993;265:E699-E707.
11.
Bader M, Zhao Y, Sander M, Lee MA, Bachmann J, Bohm M, Djavina B, Peters J, Mullins JJ, Ganten D. Role of tissue renin in the pathophysiology of hypertension in TGR (mREN2)27 rats. Hypertension. 1992;19:681-686.
12.
Moriguchi A, Brosnihan KB, Kumagai H, Ganten D, Ferrario CM. Mechanisms of hypertension in transgenic rats expressing the mouse Ren-2 gene. Am J Physiol. 1994;266:R1273-R1279.
13.
Campbell DJ, Duncan AM, Kladis A, Harrap SB. Angiotensin peptides in spontaneously hypertensive and normotensive Donryn rats. Hypertension. 1995;25:928-934.
14. Qiu HY, Valtier B, Struijker-Boudier HAJ, Levy BI. Mechanical and contractile properties of in situ localized mesenteric artery in normotensive and spontaneously hypertensive rats. J Pharmacol Toxicol Methods. 1995;33:159-170.[Medline] [Order article via Infotrieve]
15.
Qiu HY, Henrion D, Levy BI. Alterations in flow-dependent vasomotor tone in spontaneously hypertensive rats. Hypertension. 1994;24:474-479.
16. Dobrin PB, Rovick AA. Influence of vascular smooth muscle on contractile mechanics and elasticity of arteries. Am J Physiol. 1969;217:1644-1651.
17. Boonen HCM, Daemen MJAP, Eerdmans PHA, Fazzi GE, Van Kleef EM, Schiffers PMH, De Mey JGR. Mesenteric small artery changes after vasoconstrictor infusion in young rats. J Cardiovasc Pharmacol. 1993;22:388-395.[Medline] [Order article via Infotrieve]
18. Zarr JH. Biostatistical Analysis. Englewood Cliffs, NJ: Prentice Hall; 1984.
19. Campbell-Bosswell M, Robertson AL. Effects of angiotensin II and vasopressin on human smooth muscle cells in vitro. Exp Mol Pathol. 1981;35:265-276.[Medline] [Order article via Infotrieve]
20.
Geisterfer AAT, Peach MJ, Owens GK. Angiotensin II induces hypertrophy, but not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res. 1988;62:749-756.
21.
Griffin SA, Brown WCB, MacPherson F, McGrath JC, Wilson VG, Korsgaard N, Mulvany MJ, Lever AF. Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism. Hypertension. 1991;17:626-635.
22.
Daemen MJAP, Lombardi DM, Bosman FT, Schwartz SM. Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res. 1991;68:450-456.
23. Le Noble FAC, Hekking JWM, Van Straaten HWM, Slaaf DW, Struijker-Boudier HAJ. Angiotensin II stimulates angiogenesis in the chorio-allantoic membrane of the chick embryo. Eur J Pharmacol. 1991;195:305-306.[Medline] [Order article via Infotrieve]
24. Fernandez LA, Twickler J, Mead A. Neovascularization produced by angiotensin II. J Lab Clin Med. 1985;105:141-145.[Medline] [Order article via Infotrieve]
25. Morishira R, Gibbons GH, Ellison KE, Lee W, Zhang L, Yu H, Kaneda Y, Ogihara T, Dzau VJ. Evidence for direct local effect of angiotensin in vascular hypertrophy. J Clin Invest. 1994;94:978-984.
26. Peiro C, de Sagarra MR, Redondo J, Sanchez-Ferrer CF, Marin J. Vascular smooth muscle proliferation in hypertensive transgenic rats. J Cardiovasc Pharmacol. 1992;20(suppl 12):S128-S131.
27. Thybo NK, Korsgaard N, Mulvany MJ. Morphology and function of mesenteric resistance arteries in transgenic rats with low-renin hypertension. J Hypertens. 1992;10:1191-1196.[Medline] [Order article via Infotrieve]
28. Christensen KL, Mulvany MJ. Mesenteric arcade arteries contribute substantially to vascular resistance in conscious rats. J Vasc Res. 1993;30:73-79.[Medline] [Order article via Infotrieve]
29.
Owens GK, Schwartz SM, McCanna M. Evaluation of medial hypertrophy in resistance vessels of spontaneously hypertensive rats. Hypertension. 1988;11:198-207.
30. Pauletto P, Da Ros S, Capriani A, Chiavegato A, Pessina AC, Sartore S. Smooth muscle cell types at different aortic levels and in microvasculature of rabbits with renovascular hypertension. J Hypertens. 1995;13:1679-1685.[Medline] [Order article via Infotrieve]
31. Price RJ, Skalak TC. Circumferential wall stress as a mechanism for arteriolar rarefaction and proliferation in a network model. Microvasc Res. 1994;47:188-202.[Medline] [Order article via Infotrieve]
32. Glagov S, Vito R, Giddens DP, Zarins CK. Micro-architecture and composition of artery walls: relationship to location, diameter and the distribution of mechanical stress. J Hypertens. 1992;10(suppl 6):S101-S104.
33.
Dobrin PB, Baker WH, Gley WC. Elastolytic and collagenolytic studies on arteries: implications for the mechanical properties of aneurysms. Arch Surg. 1984;119:405-415.
34. White WB. Blood pressure load and target organ effects in patients with essential hypertension. J Hypertens. 1991;9(suppl 8):39-41.
35.
Baumbach GL. Effects of increased pulse pressure on cerebral arterioles. Hypertension. 1996;27:159-167.
36.
Van Gorp A, Van Ingen Schenau D, Willigers J, Hoeks AG, De Mey JGR, Struijker-Boudier HAJ, Reneman RS. A technique to assess aortic distensibility and compliance in anesthetized and awake rats. Am J Physiol. 1996;270:H780-H786.
37.
Hayoz D, Rutschmann B, Perret F, Niederberger M, Tardy Y, Mooser V, Nussberger J, Waeber B, Brunner HR. Conduit artery compliance and distensibility are not necessarily reduced in hypertension. Hypertension. 1992;20:1-6.
38.
Van Gorp AW, Van Ingen Schenau DS, Hoeks APG, Struijker-Boudier HAJ, Reneman RS, De Mey JGR. Aortic wall properties in normotensive and hypertensive rats of various ages in vivo. Hypertension. 1995;26:363-368.
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