The function of the pituitary-adrenal cortical axis be investigated in rat experimental models of adrenal regeneration (ARH), spontaneous (SHR) and stress-induced hypertension. Peptides dervied from proopiomelanocortin (POMC) will be measured in pituitary and blood with an emphasis on ACTH and pro-Gamma-melanotropins. In addition, the effect of POMC-derived peptides on adrenal function in ARH and SHR will be investigated. Thus we will examine the role of POMC-derived peptides and adrenal cortical dysfunction in animal models which bear a relationship to primary and secondary hypertension in humans. In more direct studies, the role of pro-Gamma-melanotropin in primary hyperaldosteronism and dexamethasone-suppressible hyperaldosteronism will also be examined through the measurement of POMC-derived peptides in the plasma of such patients. The role that calcium plays in the pathogenesis and/or amelioration of cardiac and renal lesions in mineralocorticoid-induced hypertension will be investigated. Techniques will be used which allow us to measure calcium in tissues and localize that cation ultrastructurally. In complementary studies the interaction of steroid hormones with vascular tissue in cell culture and in vivo will be investigated. Experiments will be carried out to study the effects of steroid hormones on vascular smooth muscle morphology, phosphorylation of contractile proteins, and calcium uptake. Parallel studies will be done with rats sensitive and resistant to steroid hypertension. The experiments are designed to determine the function of steroid hormones in vascular tissue and to explain genetic differences in sensitivity to steroid hypertension.
