Analysis of the biphasic depressor-pressor effect and tachycardia caused by neurotensin in ganglion-blocked rats

Abstract

In pentobarbital-anesthetized, vagotomized, ganglion-blocked rats, intravenous injections of NT (1–10 nmoles kg −1) evoked biphasic depressor-pressor responses. The depressor component of the response was found to predominate when 1 nmole kg −1 of NT was used, but to disappear almost completely with higher doses of the peptide. In contrast, the pressor component was more prominent with the use of higher doses of NT. Marked tachycardia usually accompanied the pressor effects of NT while little or no change of heart rate occurred during the depressor phase of the response. The depressor component of the response to 1 nmole kg −1 of NT was markedly attenuated by captopril and by nephrectomy. This result suggests that depressor responses to NT in ganglion-blocked rats are somehow linked to the activity of the renin-angiotensin system. The pressor component of the responses to NT (4 nmoles kg −1) and the associated tachycardia were reduced by 44% and 60% respectively, after ablation of adrenal glands. This result suggests that NT produces part of its cardiovascular effects in ganglion-blocked rats by stimulating the release of catecholamines from the adrenal glands. Prazosin, an alpha adrenergic receptor blocking drug, inhibited by 48% both the pressor effect and tachycardia evoked by NT while propranolol, a beta adrenergic receptor blocking drug, reduced by 67% the chronotropic effect of NT and only by 30% the pressor effect of the peptide. These results provide further evidence for the participation of catecholamines in the pressor effect and tachycardia evoked by NT in ganglion blocked rats. It also suggests that adrenal glands are the main source of the catecholamines involved in the pressor and chronotropic effect of NT. The partial blockade of the pressor effect and tachycardia of NT by low doses (1 mg kg −1) of methysergide, a serotonin receptor antagonist, suggests that serotonin and/or their receptors may also contribute to the cardiovascular effects of NT in ganglion-blocked rats. When higher doses of methysergide producing blockade of both alpha adrenergic and serotonin receptors were used, NT evoked residual pressor effects (27%) preceded by significant depressor effects. The depressor responses were resistant to blockade by effective doses of atropine, propranolol, mepyramine, cimetidine, indomethacin and disodium cromoglycate, but it were markedly attenuated by captopril, again suggesting a possible link between the depressor activity of NT and the activity of the renin-angiotensin system in ganglion-blocked rats.