Reduction by phentolamine of the hypotensive effect of methionine enkephalin in anaesthetized rabbits

Abstract

In intact rabbits anaesthetized with pentobarbitone, methionine enkephalin (Met enkephalin, 1−1,000 μg kg−1 i.v.) produced a dose‐dependent bradycardia and hypotension. The bradycardia and hypotension were antagonized by naloxone hydrochloride (1 mg kg−1), but not by naloxone methobromide (1.3 mg kg−1). Phentolamine (1 and 4 mg kg−1 i.v.) blocked both the hypotension and bradycardia produced by Met enkephalin. The inhibitory effect of phentolamine was not due to a simple hypotensive action of this drug per se because a similar degree of hypotension induced by nitroprusside (15 μg kg−1, i.v.) caused a further reduction of pressure when Met enkephalin was added. Atropine (2 mg kg−1) reduced the bradycardia but not the hypotensive response to Met enkephalin. Met enkephalin did not antagonize the vasopressor effect of exogenous noradrenaline (2–8 μg kg−1, i.v.). Met enkephalin had no significant effects in superfused thoracic aortic strips and in isolated perfused hearts of rabbits. It is concluded that the cardiovascular effects of Met enkephalin are more probably due to an action on the central nervous system, although a peripheral site of action cannot be completely excluded.

Circulating [Met]enkephalin and catecholamine responses to acute hypotension and hypertension in anaesthetized greyhounds

“…[Met]-enkephalin has been shown to produce hypotension in animals (Moore &Dowling, 1980) andHanbauer et al (1982) have demonstrated that in reserpine-treated dogs with catecholamine depletion, splanchnic nerve stimulation produced an increase in the release of adrenal enkephalins with a fall in blood pressure rather than the usual rise. Moreover Eulie & Rhee (1984) showed that in anaesthetized rabbits, [Met]enkephalin potentiated the hypotension induced by nitroprusside. The possibility then arises that endogenously produced [Metlenkephalin could contribute to the hypotensive effect of nitroprusside.…”

“…Moreover Eulie & Rhee (1984) showed that in anaesthetized rabbits, [Met]enkephalin potentiated the hypotension induced by nitroprusside. The possibility then arises that endogenously produced [Metlenkephalin could contribute to the hypotensive effect of nitroprusside.…”

“…However the mechanisms of action of opioids in inducing cardiovascular changes are not yet fully elucidated. In general the effects of administered Met-enkephalin and analogues on the cardiovascular sys-tem, especially blood pressure, depend on the animal species studied, route of administration and anaesthesia used thus causing an increase in blood pressure in conscious animals (Schaz et al, 1980;Yukimura et al:, 1981;Sander & Giles, 1982) or a decrease in blood pressure in anaesthetized animals (Wei et al, 1980;Eulie & Rhee, 1984). When tested, these effects are blocked by naloxone suggesting the involvement of opioid receptors.…”

“…Other peripheral sites of action of the enkephalins include the sympathetic nerves (Gaddis & Dixon, 1982), peripheral vasculature (Sander et al, 1981), adrenal chromaffin cells (Kumakura et al, 1980), baroreceptor reflex activity (Rubin, 1984) or through pulmonary 'JF chemoreceptors (Sapru et al, 1981). Centrally, circulating enkephalins could act on the brain opioid receptors adjacent to the circumventricular regions, areas known to have an incomplete blood-brain barrier (Holaday, 1983;Eulie & Rhee, 1984). Therefore it was of interest to us to study the circulating levels of [Metlenkephalin-like immunoreactivity (MLI) in response to cardiovascular changes.…”

Effect of Etorphine on Adrenergic Neurotransmission in the Rat and Guinea Pig Heart

“…Opioid peptides have been shown to decrease blood pressure in the pithed rat [Szabo et al, 1986], anes thetized rabbit [Eulie and Rhee, 1984] and conscious dog [Sander et al, 1981]. Further more, endogenous opioid peptides have also been implicated in the modulation of NE release in the rabbit [Schadt and Gaddis, 1985].…”