Normalization by Clonidine of Reduced Plasma Beta-endorphin and Leu-enkephalin Concentrations and Elevated Blood Pressure in Young Patients with Mild Essential Hypertension

Abstract

Evidence is accumulating that endogenous opioid peptides such as beta-endorphin and enkephalins play a role in the control of blood pressure regulation. In animals, beta-endorphin when injected intracisternally or into the nucleus of the solitary tract (NTS) causes decreases in arterial pressure and heart rate [1, 2]). Administration of the opiate antagonists naloxone and naltrexone was found to inhibit the antihypertensive effect of clonidine and alpha-methyldopa in spontaneously hypertensive rats (SHR) as well as in a subgroup of patients with essential hypertension [3, 4, 5], suggesting an interaction between the central adrenergic and opioid receptor systems. Furthermore, it was shown that clonidine increases the release of beta-endorphin immunoreactivity from the anterior pituitary [6], hypothalamus, and brain stem slices of SHR [7] and elevates plasma beta-endorphin concentrations in rats [8] and in patients with essential hypertension [9]. In contrast to the effects of beta-endorphin, the cardiovascular action of the enkephalins seems to be more variable, depending on the peptide concentrations applied, the anatomical sites of administration, and the state of the animal with respect to consciousness and strain. Thus, both intravenous administration and microinjection of enkephalins into the NTS were found to produce increases in blood pressure and heart rate [9,10]. On the other hand, in vitro studies have shown that leucine-enkephalin (leu-enkephalin) may induce hyperpolarization of sympathetic ganglia [12] and reduce the release of noradrenaline from sympathetic nerve endings [13] with subsequent vasodilation.