Renal vasoconstriction by vasopressin V_1a receptors is modulated by nitric oxide, prostanoids, and superoxide but not the ADP ribosyl cyclase CD38

Abstract

Renal blood flow (RBF) responses to arginine vasopressin (AVP) were tested in anesthetized wild-type (WT) and CD38(-/-) mice that lack the major calcium-mobilizing second messenger cyclic ADP ribose. AVP (3-25 ng) injected intravenously produced dose-dependent decreases in RBF, reaching a maximum of 25 ± 2% below basal RBF in WT and 27 ± 2% in CD38(-/-) mice with 25 ng of AVP. Renal vascular resistance (RVR) increased 75 ± 6% and 78 ± 6% in WT and CD38(-/-) mice. Inhibition of nitric oxide (NO) synthase with nitro-L-arginine methyl ester (L-NAME) increased the maximum RVR response to AVP to 308 ± 76% in WT and 388 ± 81% in CD38(-/-) (P < 0.001 for both). Cyclooxygenase inhibition with indomethacin increased the maximum RVR response to 125 ± 15% in WT and 120 ± 14% in CD38(-/-) mice (P < 0.001, <0.05). Superoxide suppression with tempol inhibited the maximum RVR response to AVP by 38% in both strains (P < 0.005) but was ineffective when administered after L-NAME. The rate of RBF recovery (relaxation) after AVP was slowed by L-NAME and indomethacin (P < 0.001, <0.005) but was unchanged by tempol. All vascular responses to AVP were abolished by an AVP V1a receptor antagonist. A V2 receptor agonist or antagonist had no effect on AVP-induced renal vasoconstriction. Taken together, the results indicate that renal vasoconstriction by AVP in the mouse is strongly buffered by vasodilatory actions of NO and prostanoids. The vasoconstriction depends on V1a receptor activation without involvement of CD38 or concomitant vasodilatation by V2 receptors. The role of superoxide is to enhance the contractile response to AVP, most likely by reducing the availability of NO rather than directly stimulating intracellular contraction signaling pathways.

Modulation of the myogenic mechanism: concordant effects of NO synthesis inhibition and O2− dismutation on renal autoregulation in the time and frequency domains

“…Animal studies have demonstrated that O 2 Ϫ dismutation by tempol attenuates renal vasoconstriction induced by ANG II, AVP, endothelin, and norepinephrine, and that this vasoconstrictor action of O 2 Ϫ may involve quenching of NO and also an action independent of NO (39,40,65). On the other hand, our laboratory (65) has shown previously that O 2 Ϫ enhances the renal vasoconstrictor action of AVP primarily by limiting the bioavailability of NO, suggesting different roles as a function of stimulus.…”

Renal Autoregulation in Health and Disease

“…Specifically, NO production affects the myogenic mechanism, as discussed in section VIC. Moreover, activation of MD cells can accelerate the rate of relaxation associated with the generation of PGE 2 (218, 1036,1334) and NO (298, 1036). Indeed, Loutzenhiser et al demonstrated later that adding exogenous NO or cGMP to the HNK preparation to more closely simulate the in vivo paracrine modulation, preferentially reduced the delay in the vasodilation response to a reduced RPP (R. Loutzenhiser, personal communication), thereby reducing the time difference between myogenic relaxation and constriction which more closely approximated to those observed in vivo.…”

Piezo1 Mediates Vasodilation Induced by Acute Hyperglycemia in Mouse Renal Arteries and Microvessels

“…V2 receptors buffer the vasoconstrictor effects of vasopressin in the kidney, however, their expression and action vary among species. [40][41][42] Although cortical arteries and VR seem to constrict to vasopressin, its effect on glomerular arterioles is weak or undetectable. 43,44 Reduced medullary blood flow due to VR constriction decreases interstitial fluid pressure and sodium excretion thereby affecting blood pressure.…”