Acute blockade of nitric oxide synthase inhibits renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats.

Abstract

Because the kidneys are vasodilated and the endogenous production of nitric oxide is increased in gravid rats, we tested whether nitric oxide mediates the renal vasodilatory response to pregnancy. Chronically instrumented, conscious rats of gestational days 12-14 were studied concurrently with age-matched virgin control animals. GFR and effective renal plasma flow (ERPF) were determined by the renal clearances of inulin and para-aminohippurate before and during acute infusion of NW-nitro-L-arginine methyl ester (NAME; 2, 20, and 50 jag/min) or NG-monomethyl-L-arginine (100 jag/min). Baseline GFR and ERPF were significantly increased, and effective renal vascular resistance was decreased by 30-40% in gravid rats compared with virgin controls. During infusion of all three dosages of NAME and NG-monomethyl-L-arginine, effective renal vascular resistance, GFR, and ERPF were equalized in the pregnant and virgin rats (the only exception being GFR during the 20 jag/min NAME infusion). When compared with virgin rats, the gravid animals were more responsive to nitric oxide synthase inhibition, showing a significantly greater decline in GFR and ERPF and rise in effective renal vascular resistance at each timepoint during the infusion of inhibitor. To exclude the possibility that nonspecific renal vasoconstriction per se led to equalization of renal function in the two groups of rats, we investigated angiotensin II. In contrast to the results observed with nitric oxide synthase inhibitors, pregnant rats were less responsive to the renal vasoconstrictory effects of angiotensin II, such that the baseline differences in renal parameters measured before infusion of the hormone were increased during the infusion. To determine whether nitric oxide synthase was inhibited to a similar extent in gravid and virgin rats, aortic and renal cortical cGMP content was assayed ex vivo at the end of inhibitor infusion. The lower 2-pag/min dose of NAME consistently reduced cGMP content of these tissues to comparable levels in the two groups of rats. In conclusion, we suggest that Receivedfor publication 20 December 1994 and accepted in revised form 14 March 1995. nitric oxide mediates reduced renal vascular resistance and hyperfiltration during pregnancy in conscious rats. (J. Clin. Invest. 1995. 96:482-490.)

New Aspects in the Pathophysiology of Preeclampsia

“…This renal vasodilatory effect does not require the presence of the ovaries (25) and is also observed during relaxin administration to male rats (26). Relaxin administration to nonpregnant female rats also diminishes the renal vasoconstrictor response to angiotensin II, similar to the dampening influence of rat gestation (25,27,28). Moreover, reduced myogenic reactivity of small renal arteries is observed after relaxin administration, analogous to vessels isolated from midterm pregnant rats (29,30).…”

The vasoconstrictor effects of L‐NAME, a nitric oxide synthase inhibitor, in pregnant rabbits

“…Therefore, we speculate that although NO may contribute to the maintenance of reduced vessel tone in some vascular regions during pregnancy (e.g. uteroplacental (Conrad et al, 1993a,b), renal (Danielson & Conrad, 1995)), the reduced total peripheral resistance, at least in rabbits, is mediated by an as yet unidentified mechanism.…”

Obstetric Nephrology

“…The proposed mechanism of relaxin involves an increase in vascular gelatinase activity, which upregulates NO-dependent vasodilation via the endothelin-B NO pathway (14). In pregnant rats, investigators have convincingly demonstrated increments in endogenous production of NO (15), and through acute or chronic inhibition of NO synthase, investigators have demonstrated abolishment of the glomerular hyperfiltration in pregnancy (16,17). Hence, NO is necessary for the hemodynamic adaptation in renal function during pregnancy, and relaxin may represent a pregnancy-specific mechanism for augmenting the effects of NO.…”