Comparative sensitivities of isolated rat renal arterioles to endothelin

Lanese, Diane M.; Yuan, B. H.; McMurtry, Ivan F.; Conger, John D.

doi:10.1152/ajprenal.1992.263.5.f894

Cited by 24 publications

(24 citation statements)

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“…The decrease in GFR may have been due to a predominant efferent arteriole vasodilation. This explanation is supported by several micropuncture 22 and in vitro microperfusion 23 studies that have found that efferent arterioles are more sensitive than afferent arterioles to ET administration. However, we again cannot rule out that changes in the ultrafiltration coefficient accounted for the changes in GFR, although this would be unusual, since most studies show either no change or decreased permeability during ET infusion.…”

Section: Relative Role Of Ang II Through Its At 1 Receptor Et No Amentioning

confidence: 75%

Interactions Between Vasoconstrictors and Vasodilators in Regulating Hemodynamics of Distinct Vascular Beds

Gómez-Alamillo¹,

Juncos²,

Cases³

et al. 2003

Hypertension

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Abstract-We examined whether interactions between angiotensin II (Ang II), endothelin (ET), nitric oxide (NO), and prostaglandins (PGs) differentially regulate perfusion to distinct vascular beds. For this, we blocked either angiotensin AT 1 or ET receptors or both and then sequentially inhibited NO and PG synthesis in anesthetized dogs. Blocking Ang II or ET had similar effects on systemic hemodynamics: Mean arterial pressure fell slightly without altering cardiac output. Blocking both caused a synergistic fall in mean arterial pressure and increased cardiac output. Pulmonary vascular resistance was not altered by blocking Ang II, ET, or both but progressively increased during NO and PG blockade in group 2 (which had unblocked ET receptors), suggesting that endogenous ET exerts pulmonary vasoconstriction that is tempered by NO and PGs. In the kidney, blocking Ang II increased regional blood flow (RBF), glomerular filtration rate (GFR), and fractional excretion of sodium (FENa). In contrast, blocking ET did not alter RBF, and it decreased GFR and FENa. Combined Ang II and ET blockade markedly increased RBF without altering GFR, and FENa was maintained at the levels as when only ET was blocked. Sequentially inhibiting NO and PGs decreased RBF when Ang II or ET were blocked but had little effect when both were blocked. Finally, Ang II or ET blockade did not alter iliac blood flow. Inhibiting NO and PGs decreased iliac blood flow when Ang II or ET but not both were blocked. These results suggest that regional differences in the interactions between endogenous Ang II, ET, NO, and PGs are important determinants in systemic, pulmonary, and regional hemodynamics. Key Words: endothelin Ⅲ angiotensin II Ⅲ nitric oxide Ⅲ prostaglandins Ⅲ hemodynamics Ⅲ natriuresis T he maintenance of mean arterial pressure (MAP) depends on a critical equilibrium between renal perfusion and systemic blood pressure. 1 In general, increments of renal perfusion pressure trigger compensatory mechanisms that tend to lower MAP, whereas the opposite occurs when renal perfusion pressure is decreased. To a large extent, these cardiorenal interactions are enacted by the participation of humoral systems such as renin angiotensin, prostaglandins (PGs), nitric oxide (NO) and as revealed in more recent studies by endothelin (ET). Because of this, numerous studies have evaluated the effects of angiotensin II (Ang II), ET, NO donors, and PGs by infusing 2-5 or blocking one or more of these vasoactive factors. 6 -10 However, the relative role that each one of these vasoactive factors plays in regulating regional hemodynamics remains incompletely understood. Therefore, the aim of the present study was to determine the relative role of endogenous Ang II, ET, NO, and PGs (as well as their interactions) in regulating systemic and regional hemodynamics (with particular emphasis on renal function) in normal anesthetized dogs. For this purpose, we blocked the effects of either Ang II with the intravenous administration of L158,810 (a selective AT 1 receptor antag...

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Section: Relative Role Of Ang II Through Its At 1 Receptor Et No Amentioning

confidence: 75%

Interactions Between Vasoconstrictors and Vasodilators in Regulating Hemodynamics of Distinct Vascular Beds

Gómez-Alamillo¹,

Juncos²,

Cases³

et al. 2003

Hypertension

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“…Concentration response curves to increasing molar concentrations of ET were previously determined by our laboratory ( 16). Using known near maximal concentrations of ET for AA ( 10 -1 M) and EA ( 10-11 M), changes in lumen diameter with ET alone were compared to changes observed with ET in the presence ofthe putative ETA receptor antagonist (Cyclo D-Asp-L-Pro-D-Val-L-Leu-D-Trp; Peptides International Inc., Louisville, KY).…”

Section: Methodsmentioning

confidence: 99%

“…Presumably, the molecular radius of such an antibody was too large to permit significant extravascular movement into the subintimal or perivascular space suggesting its primary effect likely involved the binding of circulating ET. On the other hand, there is evidence that ET released from endothelial cells acts primarily by a paracrine mechanism, binding to receptors on adjacent smooth muscle cells ( 15,16). Theoretically, such a mechanism would not be affected by an anti-ET antibody with limited access to the subintimal space.…”

Section: Introductionmentioning

confidence: 99%

Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles.

Lanese¹,

Conger²

1993

J. Clin. Invest.

205

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Recent evidence suggests that the potent constrictor peptide, endothelin (ET) has a mediating role in cyclosporine A (CsA)-related renal vasoconstriction. However, the nature of the CsA-ET interaction and effect on the renal vasculature is uncertain. The purpose of the present study was twofold: (a) to determine if CsA exposure caused direct local release of ET from the endothelium of the renal microvasculature and (b) to determine if locally generated ET has paracrine effects on the underlying vascular smooth muscle to induce vasoconstriction. Experiments were performed in isolated rat renal arterioles. First it was determined that both afferent arteriole (AA) and efferent arteriole (EA) exhibited concentration-dependent decreases in lumen diameter to increasing molar concentrations of CsA. The AA was more sensitive to the vasoconstrictive effects of CsA than the EA. Next, the blocking effect of a recently synthesized putative ETA receptor antagonist was verified in both the AA and EA, where it was found that the cyclic peptide cyclo D-Asp-L-Pro-D-Val-L-Leu-D-Trp totally inhibited the vasoconstriction observed with ET addition. Finally, the role of locally stimulated ET in CsA-induced vasoconstriction was tested by determining the effect of the ETA receptor antagonist on CsA-induced AA and EA constriction. In the AA the vasoconstrictor effect of 1011 M CsA was completely blocked by the ETA receptor antagonist. However, in contrast to AA, 10 1 M CsA in EA in the presence of the ETA receptor antagonist decreased EA lumen diameter by a mean of 41% from baseline (4.80±0.75 ,um vs 7.80±0.84 ,tm, P < 0.05). This change in lumen diameter was similar to that induced by CsA alone. These data suggest that CsA directly constricts renal microvessels. This effect is mediated by ET in the AA but not the EA. (J.

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“…Interestingly, the renal vasculature appears particularly sensitive to the vasohonstrictor effects of endothelin (Pernow et al, 1988: Lanese et al, 1992, and ET-1 can be produced in several renal cell types (Kon & Badr, 1991;Perico & Remuzzi, 1993). Since several forms of acute renal failure involve intense renal vasoconstriction, it is not surprising that endothelin has been postulated as a potential mediator.…”

Section: Introductionmentioning

confidence: 99%

Characterization of endothelin receptors in rat renal artery in vitro

Clark

Pierre

1995

British J Pharmacology

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1 The aim of this study was to investigate the function and characteristics of endothelin receptors in rat main branch renal artery in vitro.2 Endothelin(ET)-l (mean ECjO = 9.8 nM) was approximately 12 fold more potent than ET-3 (mean EC50 = 120 nM) as a contractile agonist and produced a greater maximum response. In contrast, neither of the ETB receptor-selective agonists, alanine1l'3"1 "'ET-1 nor sarafotoxin S6c, (0.1 nM-I1tM), induced any contractile effect, or any relaxant effect in endothelium-intact preparations pre-contracted with the thromboxane A2 mimetic, U-46619. Sarafotoxin S6c (30 nM) also failed to induce any further contraction in tissues pre-contracted with an ECm concentration of ET-1.3 The ETA receptor-selective antagonist, BQ123, behaved as a weak and variable antagonist of the contractile effects of ET-1 (mean pA2 estimates in the range 5.8-6.3). In contrast, BQ123 antagonized ET-3 with a potency (mean pA2= 7.6) consistent with its affinity for ETA receptors. Co-incubation of BQ123 (3 IM) with the putative ETB receptor-selective antagonist, IRL1038 (10lM), produced no greater antagonism of ET-1 responses than was induced by BQ123 (3 JsM) alone. 4 In conclusion, ETB receptors do not appear to be present in rat main branch renal artery. The contractile effects of ET-3 in this tissue seem to be mediated by ETA receptors. While ETA receptors partly mediate the contractile effects of ET-1, these data raise the possibility that a population of novel BQ123-insensitive endothelin receptors may also contribute to this response.

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Comparative sensitivities of isolated rat renal arterioles to endothelin

Cited by 24 publications

References 0 publications

Interactions Between Vasoconstrictors and Vasodilators in Regulating Hemodynamics of Distinct Vascular Beds

Interactions Between Vasoconstrictors and Vasodilators in Regulating Hemodynamics of Distinct Vascular Beds

Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles.

Characterization of endothelin receptors in rat renal artery in vitro

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