Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors

M Gerová,F Kristek,M Cebová,S Cacányiová

doi:10.1590/s0100-879x2005000600019

M Gerová, F Kristek + Show 2 more

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https://doi.org/10.1590/s0100-879x2005000600019

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Abstract

Discrepancy was found between enhanced hypotension and attenuated relaxation of conduit arteries in response to acetylcholine (ACh) and bradykinin (BK) in nitric oxide (NO)-deficient hypertension. The question is whether a similar phenomenon occurs in spontaneously hypertensive rats (SHR) with a different pathogenesis. Wistar rats, SHR, and SHR treated with NO donors [molsidomine (50 mg/kg) or pentaerythritol tetranitrate (100 mg/kg), twice a day, by gavage] were studied. After 6 weeks of treatment systolic blood pressure (BP) was increased significantly in experimental groups. Under anesthesia, the carotid artery was cannulated for BP recording and the jugular vein for drug administration. The iliac artery was used for in vitro studies and determination of geometry. Compared to control, SHR showed a significantly enhanced (P < 0.01) hypotensive response to ACh (1 and 10 microg, 87.9 +/- 6.9 and 108.1 +/- 5.1 vs 35.9 +/- 4.7 and 64.0 +/- 3.3 mmHg), and BK (100 microg, 106.7 +/- 8.3 vs 53.3 +/- 5.2 mmHg). SHR receiving NO donors yielded similar results. In contrast, maximum relaxation of the iliac artery in response to ACh was attenuated in SHR (12.1 +/- 3.6 vs 74.2 +/- 8.6% in controls, P < 0.01). Iliac artery inner diameter also increased (680 +/- 46 vs 828 +/- 28 microm in controls, P < 0.01). Wall thickness, wall cross-section area, wall thickness/inner diameter ratio increased significantly (P < 0.01). No differences were found in this respect among SHR and SHR treated with NO donors. These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in SHR and in SHR treated with NO donors, a response similar to that found in NO-deficient hypertension.

Highlights

After inhibition of nitric oxide synthase (NO synthase), there is a clear discrepancy in experimental results concerning the acetylcholine (ACh)-induced relaxation of isolated vessels in vitro and the hypotensive response in vivo in anesthetized animals
These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in spontaneously hypertensive rats (SHR) and in SHR treated with NO donors, a response similar to that found in NOdeficient hypertension
Experiments performed on conscious animals, animals under anesthesia, and under various types of anesthesia, with NO synthase inhibition and consequent increased blood pressure, have demonstrated hypotension elicited by ACh [5,6,7]

Summary

Introduction

After inhibition of nitric oxide synthase (NO synthase), there is a clear discrepancy in experimental results concerning the acetylcholine (ACh)-induced relaxation of isolated vessels in vitro and the hypotensive response in vivo in anesthetized animals. Experiments with various conduit segments of the arterial tree studied in vitro have demonstrated at-. Previous studies by our group showed paradoxically amplified ACh hypotension after a short period of time (1-2 h) and 6 weeks after NO synthase inhibition, which was accompanied by sustained high blood pressure [8]. The amplified hypotension was triggered via muscarinic receptors Bradykinin, another activator of NO synthase, induced hypotension after NO synthase inhibition accompanied by hypertension [8]

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