A HYPOTENSIVE AND BRADYCARDIAC ACTION OF GAMMA(2)-MELANOCYTE-STIMULATING HORMONE (GAMMA(2)-MSH) MICROINJECTED INTO THE NUCLEUS-TRACTUS-SOLITARII OF THE RAT

In conscious and urethane-anesthetized rats intravenously (i.v.) administered gamma(2)-melanocyte-stimulating hormone (gamma(2)-MSH), a melanotropin derived from the precursor peptide pro-opiomelanocortin (POMC), has been shown to induce a presser response combined with a tachycardia. A site of action within the hindbrain, e.g. the nucleus tractus solitarii (NTS) or the area postrema (AP), has been suggested. In order to test the postulate that gamma(2)-MSH acts within these hindbrain regions, the peptide was microinjected into various parts of the NTS and into the AP of urethane-anesthetized rats and blood pressure (BP) and heart rate (HR) were measured. Injection of gamma(2)-MSH (100-500 pmol) into the NTS resulted in a dose-dependent decrease in BP and HR rather than in the expected presser and tachycardic response which is generally found in conscious and urethane-anesthetized rats following i.v. administration of the peptide. With respect to the depressor and bradycardic effect the melanotropin was far more potent when injected into the pars commissuralis than into the medial part of the NTS. The responses were maximal after 3-4 min and lasted for about 15 min. gamma(2)-MSH had no effect when injected into the AP. It is noteworthy that also a hypotensive and bradycardic effect for gamma(2)-MSH is found in pentobarbital-anesthetized rats following i.v. administration. Therefore, we conclude that in addition to a presser and tachycardic response gamma(2)-MSH can elicit an opposite effect by interaction with structures within a discrete region in the NTS, the pars commissuralis. The occurrence of these different cardiovascular responses to gamma(2)-MSH is not necessarily surprising: in fact, the direct application of gamma(2)-MSH at the NTS-site may directly activate inhibitory pathways, whereas i.v. injection allows the peptide to reach other (brain) areas involved in cardiovascular regulation as well. A depressor effect after i.v. administration of gamma(2)-MSH can be unmasked during deep anesthesia with pentobarbital which might blunt the stimulating effects by depression of sympathetic outflow.