The proposed studies are designed to evaluate the contribution of altered adrenal and pituitary function to the pathogenesis of obesity-related hypertension. The studies will focus on the mechanisms by which increased secretion of hypertensinogenic steroids can occur and lead to hypertension. Adrenal and pituitary function will be examined in vivo and in vitro in fatty Zucker rats, Koletsky obese rats, obese ventromedial nucleus- lesioned rats, congenic spontaneous hypertensive/NIH corpulent rats and appropriate lean controls. In each rat strain, the activity and amount of key enzymes of adrenocortical hormone biosynthesis will be quantitated. The levels of mRNA encoding these enzymes will also be determined using appropriate cDNA probes. Pituitary function will be assessed by measuring and comparing in the various rat strains the levels of pro- opiomelanocortin derived peptides: ACTH, pro-gamma-MSH, alpha-MSH and beta-LPH/endorphin. In parallel and related studies we will examine the interaction of key adrenocortical steroids (glucocorticoids, mineralocorticoids and androgens) with cultured vascular smooth muscle cells isolated from control rats and rats with obesity-related hypertension. The effect(s) of steroid hormones on the content, affinity and specificity of alpha- and beta-adrenergic, insulin and calcium channel receptors will be determined. Receptor activity will be correlated with the kinetics of cAMP formation and/or phosphorylation of myosin light chain-key elements thought to be involved in smooth muscle cell contraction. These studies focus on postulated hormonal changes in obesity- associated hypertension and should provide fundamental information to explain the mechanisms involved.
| Chou, F P; Gallant, S; Brownie, A C (1991) The gene expression of cytochrome P-450(11) beta during adrenal regeneration in the rat: studies using in situ hybridization. Endocr Res 17:395-408 |
| Chou, F P; Gallant, S; Brownie, A C (1989) Cytochromes P-45011 beta, P-450scc and adrenodoxin gene expression during adrenocortical regeneration in the rat. J Endocrinol 122:403-8 |
