Effects of bestatin and phosphoramidon on the hypertensive response to physostigmine in the rat

• Published in: Fundamental & clinical pharmacology Vol. 1; no. 5; p. 307
• Main Authors: Dzoljić, E, Varagić, V M
• Format: Journal Article
• Language: English
• Published: England 01-01-1987
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacology; Blood Pressure - drug effects; Carotid Arteries; Catecholamines - pharmacology; Enkephalin, Leucine - pharmacology; Female; Glycopeptides - pharmacology; Injections, Intra-Arterial; Leucine - analogs & derivatives; Leucine - pharmacology; Male; Naloxone - pharmacology; Physostigmine - pharmacology; Rats; Rats, Inbred Strains
• ISSN: 0767-3981
• DOI: 10.1111/j.1472-8206.1987.tb00568.x

Intracarotid (IC) injection of bestatin produced a dose-dependent biphasic change in blood pressure (BP) of the rat, consisting of an initial short-lasting fall followed by a long-lasting increase. This effect was regularly depressed or abolished by IV injection of naloxone. IC injection of Leu-enkephalin also produced a biphasic BP response, with the same characteristics as that produced by IC injection of bestatin. This effect was also easily blocked by IV injection of naloxone. IC injection of bestatin significantly potentiated the BP response to IC injection of Leu-enkephalin. This potentiated response was blocked by naloxone. IC injection of both bestatin and phosphoramidon, whether separately or in combination, significantly depressed the hypertensive response to physostigmine. This depressive action of bestatin and phosphoramidon on physostigmine hypertension can be significantly antagonized or even reversed by IV injection of naloxone. IC injection of both bestatin and phosphoramidon did not affect the BP response to either acetylcholine or catecholamines. It is concluded that bestatin and phosphoramidon, injected into the carotid artery, inhibit the activity of aminopeptidase and "enkephalinase", thus producing an accumulation of enkephalins in the central nervous system. These enkephalins activate opioidergic receptors in the brain, but concomitantly produce a depression of the cholinergic-adrenergic interaction in the central nervous system, which is known to be a prerequisite for the hypertensive response to physostigmine in the rat.