Blood Pressure-decreasing Effect of Etamicastat Alone and in Combination with Antihypertensive Drugs in the Spontaneously Hypertensive Rat

Overview

Journal Hypertens Res

Specialty Cardiology & Vascular Diseases

Date 2014 Oct 10

PMID 25298210

Citations 9

Authors

Bruno Igreja

Nuno Miguel Pires

Maria Joao Bonifacio

Ana Isabel Loureiro

Carlos Fernandes-Lopes

Lyndon Christopher Wright

Patricio Soares-da-Silva

Affiliations

Soon will be listed here.

Abstract

Hyperactivation of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. This study evaluated the efficacy of etamicastat, a dopamine-β-hydroxylase (DβH) inhibitor, in controlling high blood pressure in the spontaneously hypertensive rat (SHR), either alone or in combination with other classes of antihypertensives. SHRs were administered with etamicastat by gavage, and its pharmacodynamic and pharmacokinetic properties were evaluated. Etamicastat induced a time-dependent decrease in noradrenaline-to-dopamine ratios in the heart and kidney, and had no effect on catecholamine levels in the frontal cortex of SHRs. Cardiovascular pharmacodynamic effects following administration of etamicastat alone or in combination with other classes of antihypertensive drugs were assessed by telemetry. Etamicastat was evaluated in combination with captopril, losartan, hydrochlorothiazide, metoprolol, prazosin and/or diltiazem. Etamicastat monotherapy induced a dose-dependent reduction in blood pressure without reflex tachycardia. Combination therapy amplified the antihypertensive effects of all tested drugs. In conclusion, inhibition of peripheral DβH with etamicastat, as a monotherapy or combination therapy, may constitute a valid alternative treatment for high blood pressure.

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