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

Abstract

1. Pregnancy in rats is characterized by a reduction in arterial pressure that is associated with a decreased response to vasoconstrictors. However, the responses to vasodilators in isolated vessels remain controversial and are not well established in hypertensive pregnant rats. 2. In the present study, we investigated the effect of pregnancy on the bradykinin (BK)-induced vasodilator responses of the isolated mesenteric arterial bed (MAB) from Wistar normotensive and spontaneously hypertensive rats (SHR) and determined the role of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and angiotensin-converting enzyme (ACE) in these responses. 3. Mean arterial pressure (MAP) in pregnant normotensive and pregnant hypertensive rats (93 +/- 1 and 122 +/- 2 mmHg, respectively) was lower than in non-pregnant controls (128 +/- 1 and 163 +/- 2 mmHg, respectively; P < 0.05). In MAB isolated from normotensive rats and precontracted with phenylephrine, the effects of bradykinin, acetylcholine (ACh) and nitroglycerine (NG) were not influenced by pregnancy. In contrast, the vasodilator responses to BK were significantly reduced in pregnant compared with non-pregnant SHR and seemed to be specific to BK. 4. The ACE inhibitor captopril potentiated BK vasodilator responses and abolished the differences between pregnant and non-pregnant SHR. Inhibition of nitric oxide (NO) synthase by N(G)-nitro-L-arginine methyl ester (l-NAME) significantly reduced the vasodilator effect of BK in all groups. In the presence of l-NAME plus high K+ solution (47 mmol/L), BK-induced vasodilation was completely blocked. The NO-dependent component of the responses seems to be more important in hypertensive rats and pregnancy does not modify this profile. 5. Our results suggest that increased ACE activity may be involved in the pregnancy associated reduction in vasodilator responses to BK in the MAB of hypertensive rats. Pregnancy does not modify the relative contribution of the EDHF and NO to the vasodilator effect of BK.

Role of renin–angiotensin system and oxidative status on the maternal cardiovascular regulation in spontaneously hypertensive rats

“…34 We have demonstrated in this study that the vasodilator responses induced by both Ang II and Ang-(1-7) were similar in MAB from W-P and W-NP rats. This data confirm previous findings showing the NO-dependent vasodilator effect of bradykinin and acetylcholine, 35 suggesting that endothelial function is not changed during the adaptations of normal pregnancy. However, we demonstrate that the vasodilator responses induced by Ang II and Ang-(1-7) were higher in MAB from SHR-P than in SHR-NP.…”

“…This response appears to be specific to the peptides of RAS because previous studies demonstrated a reduction in the vasodilator response induced by bradykinin in mesenteric arteries from SHR-P compared to SHR-NP while acetylcholine and nitroglycerin vasodilator responses appear to be similar among the groups. 35 Overall, these data suggest an important contribution of RAS on the hemodynamic changes and BP reduction during pregnancy in genetically hypertensive rats.…”

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

“…Maeso et al (1998) provided evidence that diminished EDHF is likely to account for the reduced relaxation to ACh associated with aging in mesenteric vasculatures from SHR and that the enhancement of ACh-induced relaxations by losartan seems to be dependent of increased NO availability. In the isolated mesenteric arterial bed from pregnant SHR, vasodilator responses to bradykinin were less than those from nonpregnant SHR, and captopril potentiated the bradykinin action and abolished the differences between pregnant and nonpregnant SHR; bradykinin-induced vasodilatation was reduced by L-NAME and was abolished in the presence of L-NAME plus high K ϩ solution (Resende et al, 2004). It was concluded that increased ACE activity may be involved in the pregnancy-associated reduction in vascular responses to bradykinin in the mesenteric arteries of hypertensive rats and that the vasodilatation seems to be mediated by NO and EDHF.…”

Characterization of the L-arginine–NO–cGMP pathway in spontaneously hypertensive rat platelets: the effects of pregnancy

“…The levels obtained from pregnant hypertensive rats were not significantly different from those obtained from the normotensive groups, which were in agreement with previous findings. 15,16,21 These results might be partially explained by an increased production of NO and prostacyclin from vascular endothelium 20 and a hyporeactivity to vasoconstrictors, 34 which may contribute to vasodilation and consequent reduction in peripheral vascular resistance. Although a specific role for NO in the induction of hemodynamic alterations in pregnancy is somewhat controversial, it is widely accepted that an excess of NO is generated by endothelial cells during normal pregnancy.…”

“…20 Conversely, the responsiveness to vasodilators such as bradykinin is decreased in resistance arteries of pregnant SHRs 21 as well as in small subcutaneous arteries and myometrial resistance arteries from women with preeclampsia. 22,23 Because bradykinin endothelium-dependent relaxation is mediated by NO and endothelium-derived hyperpolarizing factor, these findings suggest that endothelial dysfunction may contribute to the altered vasoreactivity seen in pregnant SHRs, 21 to preeclampsia and to decreased placental perfusion and its associated intrauterine growth restriction. 24 The endothelium has a key role in maintaining blood fluidity and in preventing thrombus formation.…”