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(Hypertension. 1995;26:1024-1029.)
© 1995 American Heart Association, Inc.

Articles

Role of Nitric Oxide in Modulating the Vasoconstrictor Actions of Angiotensin II in Preglomerular and Postglomerular Vessels in Dogs

Christine G. Schnackenberg; F. Clayton Wilkins; Joey P. Granger

From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.

	Abstract

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Abstract The purpose of this study was to determine the role of nitric oxide in modulating the vasoconstrictor effect of angiotensin II (Ang II) on renal segmental resistances in the dog. To achieve this objective we examined the effect of intrarenal infusions of Ang II on preglomerular and postglomerular resistances in the presence and absence of intrarenal nitric oxide synthesis inhibition established by an intrarenal infusion of N^G-nitro-L-arginine-methyl ester at 5 µg/kg per minute in dogs. The whole-kidney stop-flow technique was used. Renal artery pressure was servo-controlled at 78±2 mm Hg throughout the study. Intrarenal infusion of Ang II alone at 0.5 and 2.0 ng/kg per minute increased renal vascular resistance (0.064±0.011 and 0.171±0.030 mm Hg/mL per minute, respectively) and decreased renal blood flow (21±4 and 45±9 mL/min). Associated with these changes, glomerular hydrostatic pressure and preglomerular resistance increased slightly (1.1±0.9 and 1.6±1.8 mm Hg; 0.008±0.005 and 0.030±0.010 mm Hg/mL per minute, respectively), and postglomerular resistance increased markedly (0.046±0.011 and 0.116±0.026 mm Hg/mL per minute). When dogs were pretreated with an intrarenal infusion of the nitric oxide synthesis blocker, Ang II at 0.5 and 2.0 ng/kg per minute increased renal vascular resistance (0.271±0.058 and 1.088±0.242 mm Hg/mL per minute) and decreased renal blood flow (28±5 and 62±9 mL/min). However, in sharp contrast to vehicle pretreatment, Ang II decreased glomerular hydrostatic pressure (3.4±1.5 and 9.9±2.0 mm Hg), increased postglomerular resistance (0.122±0.029 and 0.439±0.133 mm Hg/mL per minute), and increased preglomerular resistance (0.109±0.031 and 0.487±0.099 mm Hg/mL per minute) in dogs pretreated with the nitric oxide synthesis inhibitor. In summary, these data indicate that during vehicle treatment Ang II infusion in the stop-flow kidney had a predominant effect on postglomerular resistance. However, when nitric oxide synthesis was blocked, Ang II had a profound effect on preglomerular resistance. These findings suggest that nitric oxide may play an important role in protecting mainly preglomerular vessels and to a lesser extent postglomerular vessels from Ang II–induced renal vasoconstriction in dogs.

Key Words: nitric oxide • angiotensin II • dogs • vasoconstriction • kidney

	Introduction

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Previous investigations have shown that Ang II is important in the regulation of renal hemodynamics primarily through its actions on postglomerular vessels.^{1 2 3} However, Ang II is also thought to have an effect on preglomerular vessels that may be modified by endothelium-derived factors such as NO^{4 5 6} and prostaglandins.^{7 8} Using isolated microperfused rabbit vessels Ito et al⁵ first showed evidence that local production of NO is an important determinant of afferent arteriolar tone. Similarly, Edwards and Trizna⁴ observed that rabbit afferent arterioles but not efferent arterioles synthesize and release NO in the basal state. Ito and colleagues⁶ later provided evidence that NO significantly modulates Ang II–induced vasoconstriction in isolated rabbit afferent arterioles but not efferent arterioles and suggested that NO may contribute to the differential sensitivity of the renal microvasculature to Ang II in the rabbit.

In contrast to the studies in the rabbit, investigations of the interaction between Ang II and NO in the rat renal microvasculature have provided opposing results. With an intravenous infusion of the NO synthesis inhibitor L-NMMA, Zatz and De Nucci⁹ observed that efferent arteriolar resistance increased more than afferent arteriolar resistance, suggesting a predominant effect of NO on postglomerular vessels in the rat. In addition, Ohishi et al¹⁰ observed in microvessels of rat juxtamedullary nephrons that Ang II–induced vasoconstriction of efferent and afferent arterioles was not exaggerated by NO synthesis blockade.

Our laboratory recently reported that the GFR and RBF responses to Ang II were markedly enhanced in conscious dogs that were pretreated with an intrarenal NO synthesis blocker.¹¹ GFR and RBF decreased similarly in response to Ang II in dogs pretreated with L-NAME, and these responses were reversed by treatment with L-arginine. These data suggest that NO may play an important role in protecting mainly preglomerular vessels from Ang II–induced vasoconstriction in dogs. However, no reported studies have examined the renal microvascular sites at which NO and Ang II interact in the dog. Therefore, the purpose of this study was to identify the sites at which NO protects the renal microvasculature from Ang II–induced vasoconstriction in the dog. We determined the preglomerular and postglomerular vessel responses to intrarenal Ang II infusion in the presence and absence of intrarenal NO synthesis blockade, established by intrarenal infusion of L-NAME in dogs. We used the whole-kidney stop-flow technique to measure preglomerular and postglomerular resistances in dogs as previously described.^{12 13}

	Methods

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Animal Preparation
Experiments were performed in nine mongrel dogs that were maintained on a daily fixed sodium diet and that had endogenous Ang II blocked. For 2 days before the experiment dogs received the angiotensin-converting enzyme inhibitor captopril (Sigma Chemical Co) at 100 mg/d and a daily fixed sodium diet (two cans of H/D, Hill's Pet Products, and 150 to 175 mmol NaCl supplement). All protocols were approved by the Institutional Animal Care and Use Committee of the University of Mississippi Medical Center and were performed according to the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health as well as the guidelines of the Animal Welfare Act.

On the day of the experiment dogs were anesthetized with an initial dose of pentobarbital sodium (30 mg/kg IV) followed by a continuous intravenous infusion of 4 mg/kg per hour to maintain a constant level of anesthesia throughout the experiment. Tygon catheters (Norton Co) were implanted in the femoral vein, femoral artery, and abdominal aorta just distal to the origin of the renal arteries for infusion, arterial blood sampling, and renal artery pressure measurement, respectively. The left kidney was exposed through a retroperitoneal flank incision, and small sections of the abdominal aorta, renal artery, and ureter were isolated. The ureter was cannulated with a Tygon catheter and later connected to a Statham pressure transducer (Sema Inc) for measurement of ureteral stop-flow pressure. An inflatable silicone elastomer occluder was implanted on the aorta proximal to the origin of the renal arteries and attached to a bidirectional syringe infusion pump for servo-control of renal artery pressure as previously described.¹⁴ RBF was measured with an electromagnetic flow probe placed on the renal artery and connected to a square-wave flowmeter (Carolina Medical Electronics). Proximal to the electromagnetic flow probe, a 23-gauge curved needle was inserted into the renal artery and maintained patent by infusion of 0.5 mL/min isotonic saline. Renal artery pressure, RBF, and ureteral stop-flow pressure were continuously recorded on a polygraph (Grass Medical Instruments).

During all experiments endogenous Ang II formation was blocked with the use of captopril infused at a rate of 15 µg/kg per minute IV throughout the experiment. Captopril infusion was necessary for assessment of the actions of exogenous Ang II infusion in the absence of changes in endogenous Ang II formation. To verify converting enzyme blockade, we administered a 5-µg bolus of Ang I and observed no significant changes in systemic arterial pressure or RBF. To quantify preglomerular and postglomerular resistances during Ang II infusions, we used the whole-kidney stop-flow technique as previously described.^{12 13} Briefly, a 300-mL priming dose of 6% mannitol solution was given intravenously followed by a sustaining infusion at 2.0 mL/min to induce and maintain diuresis. After 15 minutes of mannitol infusion and a marked diuresis, the ureter catheter was occluded and attached to the pressure transducer. The ureteral stop-flow pressure was then allowed to stabilize. Earlier studies had suggested that glomerular hydrostatic pressure is maintained near normal levels during ureteral occlusion only when renal perfusion pressure is reduced to the lower limits of autoregulation.¹⁵ Therefore, renal artery pressure was servo-controlled at 79±1 mm Hg throughout the protocol for maintenance of a normal glomerular hydrostatic pressure during stop-flow ureteral occlusion. After ureteral pressure was stabilized, we measured the arteriovenous extraction of ¹²⁵I-iothalamate and found GFR not to be significantly different from zero.

GFR was determined by the renal arteriovenous extraction of ¹²⁵I-iothalamate (Glofil, Isotex Diagnostics). A priming dose of 0.45 µCi/kg of ¹²⁵I-iothalamate was injected intravenously followed by a sustaining dose of 0.003 µCi/kg per minute in isotonic saline infused at 1.0 mL/min. GFR was calculated as GFR=(1-Hct)xRBFx(A-V)/A, where Hct is systemic arterial hematocrit measured by the microcapillary technique and A and V are the systemic arterial and renal venous plasma concentrations of ¹²⁵I-iothalamate, respectively. GFR was not significantly different from zero during vehicle treatment (0.31 mL/min) and during intrarenal L-NAME infusion (0.99 mL/min). Plasma protein was measured with a refractometer (American Optical Corp) and was not significantly altered during either vehicle or L-NAME treatment.

Experimental Protocol
The protocol consisted of periods of control and intrarenal Ang II infusions in the absence and presence of intrarenal NO synthesis inhibition. The protocol began with a 20-minute control period during which dogs were infused with isotonic saline vehicle via the renal artery (0.5 mL/min). Ang II was then infused intrarenally at 0.5 ng/kg per minute (n=9) for 20 minutes, followed by Ang II infused intrarenally at 2.0 ng/kg per minute (n=7) for another 20 minutes. After the Ang II infusions were completed and the dogs had recovered, the second stage of the protocol began with blockade of NO synthesis within the kidney. L-NAME was infused intrarenally at 5 µg/kg per minute. We have previously shown in several studies that this L-NAME dose infused via the renal artery blocks endothelium-dependent vasodilation in the dog.^{11 16 17} After a 60-minute pretreatment period with L-NAME, 20-minute periods of control and Ang II infusions followed. During each 20-minute period renal artery pressure was servo-controlled and ureteral stop-flow pressure and RBF were continuously measured. Duplicate samples of systemic arterial and renal venous blood were taken at the end of each period for determination of GFR, plasma protein concentration, and hematocrit.

Analytic Methods
The methods and assumptions used to calculate glomerular hydrostatic pressure, preglomerular resistance, and postglomerular resistance in normal kidneys have been described in detail.^{18 19} Briefly, GFR is expressed as GFR=K_f(P_g-P_t-_g), where K_f is the glomerular capillary filtration coefficient, P_g is glomerular hydrostatic pressure, P_t is proximal tubule hydrostatic pressure, and _g is glomerular oncotic pressure. When GFR is zero, P_g=_g+P_t. When GFR and tubular reabsorption are both zero under steady-state conditions, there is no flow and thus no drop in hydrostatic pressure along the renal tubules. Thus, P_t is theoretically equal to the ureteral stop-flow pressure. Selkurt et al²⁰ reported that ureteral occlusion for 15 to 20 minutes during mannitol diuresis almost completely stops GFR so that there is no detectable pressure gradient along the renal tubules and P_t is essentially the same as the stop-flow ureteral pressure. Therefore, in this study we continuously measured ureteral stop-flow pressure after 20 minutes of ureteral occlusion and found GFR not to be significantly different from zero (0.31 mL/min). When GFR is zero, glomerular oncotic pressure is equal to the systemic arterial colloid osmotic pressure, which can be calculated from measurements of arterial plasma protein concentration. Details of the relationship between plasma protein concentration and colloid osmotic pressure were previously explained.²¹

Finally, assuming P_g=_g+P_t, we calculated preglomerular (R_a) and postglomerular (R_e) resistances as R_a=(RAP-P_g)/RBF and R_e=(P_g-P_rv)/RBF, where RAP is renal artery pressure and P_rv is renal venous pressure, which is assumed to be constant. Throughout this study the ureteral stop-flow pressure technique will be used as an indirect method of measuring preglomerular and postglomerular resistances in dogs.

Statistical Analysis
All data are expressed as mean±SE. The responses to intrarenal Ang II treatment were compared with control conditions with the use of repeated-measures ANOVA and Dunnett's t test. Values of P<.05 were considered to be statistically significant. The absolute change from control values of preglomerular and postglomerlular resistances in response to Ang II was compared between treatments (vehicle or L-NAME) with a paired Student's t test. Values of P<.05 or P<.001 were considered to be statistically significant.

	Results

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Fig 1 illustrates the RBF response in control conditions and during intrarenal Ang II infusion at 0.5 and 2.0 ng/kg per minute before (vehicle) and after (L-NAME) intrarenal NO synthesis inhibition in dogs with stop-flow kidneys. In response to intrarenal infusions of Ang II, RBF decreased in a dose-dependent manner. During vehicle treatment, RBF decreased by 10% (21±4 mL/min) and 25% (45±9 mL/min) in response to the low and high Ang II infusion rates, respectively. RBF decreased from a control value of 184±18 mL/min to 165±17 and 138±16 (P<.05) and reached statistical significance at the 2.0 ng/kg per minute Ang II infusion rate. Intrarenal NO synthesis blockade alone decreased RBF by 29% to 112±12 mL/min (P<.05). In dogs pretreated with L-NAME Ang II infusion at 0.5 and 2.0 ng/kg per minute decreased RBF by 21% (28±5 mL/min, P<.05) and 58% (62±9 mL/min, P<.05), respectively. RBF decreased from a control value of 112±12 mL/min to 89±10 and 47±9 (P<.05) in response to Ang II infusions, respectively. Overall, intrarenal L-NAME infusion decreased baseline RBF by 25 mL/min, but NO synthesis blockade also potentiated the decreases in RBF that were observed in response to intrarenal Ang II infusion.

View larger version (18K): [in this window] [in a new window]   Figure 1. Bar graphs show changes in RBF and glomerular hydrostatic pressure in response to control conditions and intrarenal infusion of Ang II at 0.5 and 2.0 ng/kg per minute before (vehicle) and after intrarenal NO synthesis inhibition with L-NAME. *P<.05 vs control period.

The glomerular hydrostatic pressure response to Ang II during vehicle and L-NAME treatment is also illustrated in Fig 1. Glomerular hydrostatic pressure (P_g) increased slightly from a control value of 61±2 to 62±2 mm Hg in response to the Ang II infusions during vehicle treatment. However, in dogs pretreated with an intrarenal NO synthesis inhibitor, Ang II infusions of 0.5 and 2.0 ng/kg per minute decreased P_g markedly from a control value of 61±2 mm Hg by 6.5% to 57±2 and by 20% to 49±2 (P<.05), respectively.

Fig 2 illustrates the renal microvascular response to Ang II during both vehicle and L-NAME treatments. Intrarenal Ang II infusion at 0.5 and 2.0 ng/kg per minute had a relatively small effect on preglomerular resistance during vehicle treatment. Preglomerular resistance increased from a control value of 0.100±0.023 mm Hg/mL per minute to 0.106±0.024 and 0.133±0.026 (P<.05), respectively, during vehicle treatment. Intrarenal NO synthesis blockade alone increased preglomerular resistance from 0.116±0.026 to 0.173±0.037 mm Hg/mL per minute (P<.05). In contrast to the response during vehicle treatment the preglomerular response to Ang II was markedly increased after pretreatment with the NO synthesis inhibitor L-NAME. Intrarenal infusion of Ang II at 0.5 and 2.0 ng/kg per minute increased preglomerular resistance from 0.173±0.037 mm Hg/mL per minute by 59% to 0.272±0.057 and by 341% to 0.752±0.133 (P<.05), respectively, after pretreatment with L-NAME.

View larger version (18K): [in this window] [in a new window]   Figure 2. Bar graphs show changes in preglomerular and postglomerular resistances in response to control conditions and intrarenal infusion of Ang II at 0.5 and 2.0 ng/kg per minute before (vehicle) and after intrarenal NO synthesis inhibition with L-NAME. *P<.05 vs control period.

Fig 2 also depicts the postglomerular response to Ang II before and after intrarenal NO synthesis inhibition. The postglomerular resistance response to Ang II infusion was enhanced after intrarenal NO synthesis blockade; however, the potentiation was not as great as that found at preglomerular sites. During vehicle treatment postglomerular resistance increased from the control value of 0.282±0.030 mm Hg/mL per minute by 18% to 0.336±0.036 and by 43% to 0.399±0.052 in response to intrarenal Ang II infusions of 0.5 and 2.0 ng/kg per minute, respectively. Intrarenal NO synthesis blockade alone increased postglomerular resistance by 21% from 0.348±0.048 to 0.481±0.076 mm Hg/mL per minute (P<.05). Furthermore, after intrarenal NO synthesis blockade Ang II increased postglomerular resistance from 0.481±0.76 mm Hg/mL per minute by 21% to 0.577±0.097 and by 102% to 0.968±0.180 (P<.05).

Fig 3 summarizes the absolute change from control values of preglomerular and postglomerular resistances during intrarenal Ang II infusions of 0.5 and 2.0 ng/kg per minute in the presence and absence of intrarenal NO synthesis blockade. The absolute change in preglomerular resistance in response to intrarenal Ang II infusion at 0.5 ng/kg per minute was 16.5-fold higher in dogs pretreated with L-NAME than during vehicle treatment (0.006 versus 0.099 mm Hg/mL per minute, P<.05). The change in preglomerular resistance in response to Ang II infusion at 2.0 ng/kg per minute was 17.5-fold higher during L-NAME treatment than during vehicle treatment (0.033 versus 0.579 mm Hg/mL per minute, P<.001). In marked contrast, L-NAME pretreatment increased the postglomerular response to Ang II at 0.5 ng/kg per minute by only 2.2-fold (0.044 versus 0.096 mm Hg/mL per minute, P<.05) and by 4.1-fold after Ang II infusion at 2.0 ng/kg per minute (0.117 versus 0.487 mm Hg/mL per minute, P<.05).

View larger version (17K): [in this window] [in a new window]   Figure 3. Bar graphs show absolute changes from control values of preglomerular and postglomerular resistances in response to intrarenal infusion of Ang II at 0.5 and 2.0 ng/kg per minute in dogs with stop-flow kidneys after treatment with vehicle and L-NAME infused intrarenally at 5 µg/kg per minute. *P<.05, **P<.001 vs vehicle.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The results of this study indicate that NO may play an important role in protecting the renal microvasculature from excessive Ang II–induced vasoconstriction in the dog. Furthermore, this protective effect of NO appears to be greater at preglomerular than postglomerular sites. Intrarenal L-NAME infusion increased the preglomerular response to Ang II at 0.5 and 2.0 ng/kg per minute by 16.5-fold and 17.5-fold, respectively. However, intrarenal NO synthesis blockade increased the postglomerular response to Ang II by 2.2-fold and 4.1-fold.

Using micropuncture techniques, investigators have shown that Ang II infusion in normal animals with kidney function intact causes increases in the resistance of both preglomerular and postglomerular vessels.^{22 23} However, some of the increases in preglomerular resistance are thought to be primarily due to either a pressure-dependent myogenic response²³ or to activation of a tubuloglomerular feedback mechanism that compensates for high levels of Ang II.²⁴ In our study when tubuloglomerular feedback was blocked by occlusion of the ureter during mannitol diuresis and when renal artery pressure was maintained constant by servo-control, relatively little change in preglomerular resistance occurred in response to Ang II infusion during vehicle treatment. In marked contrast, intrarenal infusion of Ang II caused marked increases in postglomerular resistance. These results are similar to those reported by Olsen et al¹³ in a study using the same ureteral stop-flow technique in dogs. These investigators did not find any significant change in preglomerular resistance in response to intravenous Ang II infusion in dogs with ureteral occlusion and found postglomerular resistance to increase.

The exact reason Ang II constricts postglomerular vessels to a greater extent than preglomerular vessels has been a subject of considerable interest because of its implications in the regulation of renal hemodynamics. One possible mechanism to explain the preglomerular response to Ang II is a lack of Ang II receptors on the preglomerular vessels. However, it is still unknown whether preglomerular vessels repond less to Ang II because of a paucity of receptors. Furthermore, studies suggest that preglomerular vessels can constrict markedly after Ang II treatment under certain conditions.^{13 25} Another possible mechanism for the lack of a potent effect of Ang II on preglomerular vessels under normal conditions is that local autacoid factors are produced in significant quantities in these vessels, and these factors modulate the preglomerular vasoconstrictor response to Ang II. Results from the present study indicate that NO may play an important role in protecting the preglomerular and postglomerular vessels from Ang II vasoconstriction in the dog. For example, during vehicle treatment Ang II at 2.0 ng/kg per minute markedly increased postglomerular resistance by 43% while increasing preglomerular resistance by 30%. However, when Ang II was infused in dogs after pretreatment with intrarenal NO synthesis blockade, preglomerular resistance increased by 341% and postglomerular resistance by 102%. These findings support an important role for NO in protecting mainly the preglomerular vessels but also postglomerular vessels from excessive Ang II–induced vasoconstriction in the dog.

There are several explanations for the mechanisms by which NO protects preglomerular vessels from the powerful direct constrictor actions of Ang II. First, Ang II may stimulate NO synthesis at preglomerular sites. Enhanced NO production may then offset the vasocontrictor action of Ang II. Second, basal NO synthesis may be higher in preglomerular than postglomerular vessels. The increased basal NO synthesis in preglomerular vessels may modulate the vasoconstrictor action of Ang II through changes in vascular smooth muscle postreceptor events. Ito et al⁵ have shown that L-NAME caused a greater decrease in luminal diameter in afferent than efferent arterioles in isolated perfused rabbit arterioles, suggesting that NO synthesis is greater in afferent than efferent arterioles. Further studies will be needed for determination of the exact mechanisms whereby NO protects the preglomerular vessels more than the postglomerular vessels from Ang II vasoconstriction.

To measure preglomerular and postglomerular resistances in vivo, we used the whole-kidney stop-flow technique in dogs. This model allows for measurement of ureteral stop-flow pressure when GFR is zero. From the measurement of ureteral stop-flow pressure, plasma protein concentration, renal artery pressure, and RBF, glomerular hydrostatic pressure and renal segmental resistances are calculated. One advantage of this method is that it eliminates any indirect actions of Ang II that may have otherwise contributed to renal microvascular resistance. Intrarenal actions of Ang II include changes in GFR and proximal tubule reabsorption, both of which could have altered preglomerular resistance via the tubuloglomerular feedback mechanism. Therefore, to assess the direct actions of Ang II on renal segmental resistance in the presence and absence of intrarenal NO synthesis blockade, we used a model in which the myogenic and tubuloglomerular feedback mechanisms were blocked. Renal artery pressure was maintained constant to eliminate a myogenic response to Ang II, and GFR was made to be zero to block the tubuloglomerular feedback mechanism. Another advantage to the use of this model for determination of the renal segmental responses to Ang II is that it is an integrated response to Ang II of the nephrons. In this technique no one single nephron or area of nephrons is singled out for analysis.

Obviously, any experimental technique has limitations. One is that the stop-flow technique may not quantitatively mimic the interaction between NO and Ang II that occurs in normal conscious animals. However, the renal hemodynamic response to Ang II before and after intrarenal NO synthesis blockade in dogs with stop-flow kidneys is similar to that in conscious dogs.¹¹ In addition, we were unable to determine whether the changes in preglomerular resistance in this study were located in the afferent arteriole or interlobular artery. Another limitation of the whole-kidney stop-flow technique is that it is a model in which local production of vasoactive substances, such as prostaglandins, may be enhanced.¹² Although prostaglandins appear to play a role in modulating the actions of Ang II in the renal microvasculature,⁸ this interaction appears to be less quantitatively profound than the interaction between Ang II and NO that we found. Furthermore, like any technique whose purpose is to measure renal microvascular resistance, the stop-flow kidney technique measures preglomerular and postglomerular resistances indirectly. Finally, data from Chevalier et al²⁶ suggest that ureteral occlusion for 24 hours increases renal NO production in rats. However, if NO production is stimulated by acute ureteral occlusion in the dog, then NO synthesis blockade would have had an even greater effect on renal hemodynamics in dogs with stop-flow kidneys than in dogs under normal conditions. In fact, previous studies in anesthetized and conscious dogs have shown a renal hemodynamic response to intrarenal L-NAME infusion similar to what we have shown in dogs with ureteral occlusion. Therefore, we do not believe that short-term ureteral occlusion had a marked effect on renal NO synthesis production in dogs. Overall, despite the limitations mentioned above our results clearly demonstrate that the actions of Ang II on preglomerular vessels are markedly enhanced by intrarenal NO synthesis inhibition. These findings are consistent with our previous findings in conscious dogs.¹¹

In summary, these data indicate that during vehicle treatment Ang II in the stop-flow kidney had a predominant effect on postglomerular resistance. However, when NO synthesis was blocked, Ang II had a dramatic effect on preglomerular resistance. These findings suggest that under normal conditions the efferent arteriole is more sensitive to Ang II than the afferent arteriole. However, under conditions in which renal production of NO is reduced, the afferent arteriole becomes more sensitive to Ang II than the efferent arteriole. NO appears to play an important role in protecting mainly preglomerular vessels and to a lesser extent postglomerular vessels from Ang II–induced renal vasoconstriction in dogs.

	Selected Abbreviations and Acronyms

 

Ang I, II = angiotensin I, II GFR = glomerular filtration rate L-NAME = NG-nitro-L-arginine methyl ester NO = nitric oxide RBF = renal blood flow

	Acknowledgments

 
This work is supported in part by National Institutes of Health grants HL-38499 and HL-51971. Christine Schnackenberg is an Arthur C. Guyton Fellow. We thank Rong Chen and Stuart Williams for their excellent technical support.

	Footnotes

 
Reprint requests to Joey P. Granger, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216. E-mail jpg@fiona.umsmed.edu.

Received June 18, 1995; first decision August 18, 1995; accepted August 30, 1995.

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