The Role of Angiotensin Converting Enzyme and Nitric Oxide in the Enhanced Systemic Depressor Responses to Bradykinin in Pregnant Rats

Abstract

1. In the present study we have examined the effects of angiotensin I converting enzyme (ACE) inhibition and nitric oxide (NO) synthesis inhibition on bradykinin (BK) depressor responses in pregnancy in both Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Ramipril (10 mg/kg, i.v.) significantly reduced mean blood pressure (MBP) in all animals. Further administration of L-nitro-arginine (L-NOARG, 20 mg/kg, i.v.) increased MBP to a less extent in pregnant WKY and to a similar level in pregnant SHR compared with their non-pregnant controls (controls), respectively. 3. Systemic depressor responses to BK were increased in pregnant WKY and were unchanged in pregnant SHR as compared with their controls. Ramipril (10 mg/kg, i.v.) potentiated BK responses in all groups, and abolished the differences between pregnant and non-pregnant WKY. Further administration of L-NOARG (20 mg/kg, i.v.) did not further influence BK responses in all groups. 4. The results suggest that systemic depressor responses to BK are enhanced in pregnant WKY and unchanged in pregnant SHR. Decreased ACE activity may contribute to enhanced systemic depressor responses to BK in pregnant WKY.

Captopril Reverses the Reduced Vasodilator Response to Bradykinin in Hypertensive Pregnant Rats

“…The reduced plasma ACE activity observed in pregnant normotensive rats 39 may explain the increased depressor responses to BK in pregnant compared with non‐pregnant normotensive rats and may contribute to a physiological adaptation in normal pregnancy. However, it does not seem to happen in SHR, because the systemic depressor responses to BK are unchanged in pregnant compared with non‐pregnant SHR 15 . Although we did not measure ACE activity directly in the present study, vascular ACE activity has been reported to be increased in mesenteric arteries and the aorta of different models of hypertension 33,40 compared with plasma ACE activity, supporting an important influence on BK metabolism and vascular response.…”

“…In isolated mesenteric arteries of normal pregnant rats, vasodilation induced by bradykinin (BK) is increased, 9 not altered 7 or is reduced 13 compared with non‐pregnant rats, in contrast with the increased depressor response to BK in vivo. 14,15 Despite the controversies, an increased response to vasodilators could account for the observed decrease in blood pressure in mid‐gestation in humans and on the days before partum in the rat as a physiological adaptation to normal pregnancy. Moreover, little is known about the influence of hypertension on vascular reactivity to endothelium‐dependent vasodilators during pregnancy, 16,17 especially BK.…”

“…Although endothelium‐derived nitric oxide (NO) has been proposed to participate in the responses to vasodilators, 7,19,20 there is no evidence for a role of NO or endothelium‐derived hyperpolarizing factor (EDHF) in the vasodilator response to BK in the mesenteric arterial bed (MAB) of normotensive and hypertensive pregnant rats. Furthermore, because angiotensin‐converting enzyme (ACE) is a key enzyme responsible for BK degradation, 21 altered ACE activity must modify BK responses in isolated vessels, as reported in vivo 15 in normotensive pregnant rats. Thus, the aim of the present study was to determine the effect of pregnancy on BK‐induced vasodilator responses in Wistar normotensive and spontaneously hypertensive rats (SHR) and to examine the role of NO, EDHF and ACE on the eventual modifications of these responses.…”