GAMMA MSH AND THE CARDIOVASCULAR RESPONSE TO STRESS

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Increased secretion of pituitary pro-opiomelanocortin (POMC) peptides has been found in many forms of stress. We have recently reported that a relatively new class of POMC peptides, the gamma MSH's have unique cardiovascular activities, which include sympathetic nervous system activation and parasympathetic nervous system inhibition. We propose to investigate the role of Gamma MSH peptides in the cardiovascular effects of an unavoidable light-tone-footshock paradigm. The monitored cardiovascular parameters will be arterial pressure, heart rate, regional vascular resistance, and baroreceptor function. Our experiments will include: i. potentiation of stress-induced cardiovascular alterations by Gamma MSH infusions: ii. blunting to stress-induced cardiovascular effects by neurointermediate lobectomy (NLx) (elimination of a major peripheral POMC system), and in other rats, combining NLx with arcuate nucleus lesions (elimination of a major part of the CNS Gamma MSH system) (to demonstrate that the effects of these lesions are specifically due to reductions in Gamma MSH peptides, we will attempt to restore the deficits with Gamma MSH infusions); iii. radioimmunoassay of circulating POMC peptides, including Gamma MSH, in an attempt to assess intermediate lobe activity in stress and correlate it to one or more of our cardiovascular parameters; and iv. potentiation of the cardiovascular effects of stress by intermittent volume-expansion with saline. There is evidence that states of hydrominral inbalance increase the secretion of intermediate lobe hormones. The existence of a hypophyseal natriuretic hormone has been postulated but never identified. We have found the Gamma MSH peptides have natriuretic activity at doses significantly below those which produce cardiovascular effects. The potentiation by saline-expansion of a stress-induced MAP elevation could be attributed to common activation of a single pressor system. The possibility that peripheral, and possibly central, Gamma MSH peptides may be this factor will be investigated by using NLx in an attempt to block the pressor effects of saline expansion in stress. We will also measure circulating POMC peptides (including Gamma MSH) when stress and volume expansion are combined to demonstrate enhanced intermediate lobe secretion. These experiments are designed to explore the possibility that the cardiovascular activities of a new class of POMC derived peptides may play an important role in the autonomic nervous system response to stress.