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

Abstract

1 We have used anaesthetized, acutely instrumented non-pregnant (NP) and late pregnant (P) New Zealand white rabbits to examine the possible role of nitric oxide (NO) in the pregnancy-induced fall of vascular tone and arterial pressure. Systemic, renal and pulmonary vascular resistance, as well as plasma concentrations of cyclic GMP (PcGMP) were compared before and after the inhibition of NO synthesis by N0-nitro-L-arginine methyl ester (L-NAME). 2 P rabbits had lower baseline total peripheral resistance (TPR), mean arterial pressure (MAP) and higher PcGMP than NP controls (all P<0.05 or less). L-NAME (1, 10, 50 mg kg-', i.v.) resulted in dose-dependent elevation of TPR in both groups. However, the absolute, as well as percentage increases in TPR were greater (P<0.05) in NP than in P rabbits.. 3 Cardiac output (CO) was reduced more (P<0.01) by NO inhibition in NP than P rabbits. Therefore, despite the smaller increase in TPR, the elevation of MAP was greater (P<0.001) in P than NP rabbits. After L-NAME, NP rabbits developed more severe bradycardia and a greater increase of pulmonary vascular resistance which might have contributed to the more pronounced reduction of CO. 4 PcGMP increased in both groups following L-NAME, but more (P<0.01) in NP than P rabbits. 5 Infusion of acetylcholine (ACh, 0.02 tmol 1' kg-') reduced MAP and TPR more (both P<0.05) in NP than P rabbits and L-NAME reduced the ACh-induced depressor response only in NP rabbits. 6 These results suggest that the low vascular tone and arterial pressure in pregnant rabbits is not mediated by NO.

Does nitric oxide contribute to the basal vasodilation of pregnancy in conscious rabbits?

“…7]. Similar trends can be found in the other previous acute studies of cardiac output (8,16); in both cases, different conclusions would have been made depending on whether resistance or conductance changes were assessed.…”

“…Only limited previous studies of the potential differential effects of NOS blockade on cardiac output and therefore total peripheral conductance or resistance have been performed. Studying acutely prepared, anesthetized rabbits, Losonczy et al (16) reported that L-NAME produced smaller absolute and percent increases in total peripheral resistance in pregnant rabbits and concluded that NO does not mediate the low vascular tone of pregnancy. Fiol et al (8) studied the effects of L-NAME in conscious ganglion-blocked pregnant and nonpregnant rats but failed to statistically compare between groups the effects of L-NAME on cardiac output or total peripheral resistance.…”

Demonstration of the existence of nitric oxide‐independent as well as nitric oxide‐dependent vasodilator mechanisms in the in situ renal circulation in near term pregnant rats

“…Since intravascular¯ow is a substantial stimulus for endogenous NO synthesis (Miller & Vanhoutte, 1988) this may enhance the contribution of endogenous NO to renal vasodilatation in mid pregnancy. In contrast, in our experiments and those of Losonczy et al (1996), which were conducted close to term at 18 to 20 days gestation, renal blood¯ow and¯ow-induced changes in NO synthesis may have returned towards normal, leaving non-NO mediated mechanisms to predominate. Further investigations with animals at di erent gestational stages may help to clarify this issue.…”

“…Our ®ndings and those of Losonczy et al (1996) di er in some respects from those of Danielson & Conrad (1995) for they used chronically instrumented, conscious 12 ± 14 day pregnant rats and showed that baseline glomerular ®ltration rate (GFR) and e ective renal plasma¯ow (ERPF) were signi®cantly increased, and e ective renal vascular resistance was decreased by 30 ± 40% compared with nonpregnant controls. Moreover, during acute infusion of L-NAME (2 ± 50 mg min 71 ) or N G -monomethyl-L-arginine (L-NMMA, 100 mg min 71 ), e ective renal vascular resistance, GFR and ERPF were equalized in pregnant and nonpregnant rats (the only exception being GFR during the 20 mg min 71 L-NAME infusion), because pregnant rats showed a greater decline in GFR, ERPF and elevation in e ective renal vascular resistance at each timepoint during the infusion of the NO synthesis inhibitor.…”

Sexual dimorphism in renal ischemia-reperfusion injury in rats: Possible role of endothelin

“…Animals had free access to standard rat chow and tap water. All experiments were approved by a govern-sure renal blood flow (RBF; Transonic Flowmeter 101, Transonic Systems, NY, NY, USA) [24]. Total peripheral mental committee on animal welfare.…”