The cardiovascular response to epicardial application of neurotensin in guinea pigs.
Topical application of picomoles of neurotensin (NT) on the surface of the left ventricle (epicardial application) of anesthetized guinea pigs evoked dose-dependent pressor effects and tachycardia. The pressor response to epicardial NT was attenuated by pentolinium, a mixture of phentolamine and propranolol, or by guanethidine. However it was not affected by indomethacin, atropine or by a mixture of mepyramine and cimetidine. The tachycardia caused by epicardial NT was not modified by any of the aforementioned drugs. Both the pressor effects and tachycardia elicited by epicardial application of NT were markedly inhibited by chronic treatment of guinea pigs with capsaicin, and by topical application of lidocaine or tetrodotoxin to the surface of the left ventricle. Epicardial application of calcitonin gene-related peptide (CGRP), substance P (SP) or capsaicin also elicited tachycardia and either a decrease (CGRP and SP) or increase of blood pressure (capsaicin) in anesthetized guinea pigs. Epicardial application of NT, CGRP, or capsaicin in isolated, perfused hearts of guinea pigs also caused tachycardia. Together, these results suggest that the pressor responses to topical application of NT on the surface of the left ventricle in anesthetized guinea pigs are partially reflex in nature and likely to result from the stimulation by NT of cardiac sympathetic, capsaicin-sensitive, sensory nerve endings, whereas the tachycardia caused by epicardial NT appears to be due both to direct and indirect effects of NT on ventricular muscle cells. The possible participation of CGRP and/or SP in the chronotropic effect of NT applied on the epicardium, and their putative role as neurotransmitter of cardiac, capsaicin-sensitive, sensory neurons are discussed.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology; D009496:Neurotensin / Q000008:administration & dosage / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D014628:Vagotomy
D009479:Neuropeptides; D000804:Angiotensin II; D013373:Substance P; D009496:Neurotensin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin