EVIDENCE THAT ENDOGENOUS VASOACTIVE-INTESTINAL-PEPTIDE (VIP) PLAYS A ROLE IN THE MAINTENANCE OF THE GROWTH AND STEROIDOGENIC CAPACITY OF RAT ADRENAL ZONA GLOMERULOSA

The effects of a 7-day intraperitoneal infusion with VIP (0.03 nmol.kg (-1).min(-1)) and its antagonist [4-Cl-D-Phe(6),Leu(17)]-VIP (VIP-A; 3 nmol.kg(-1).min(-1)) were studied in sham and bilaterally adrenalecto mized rats bearing ACTH and angiotensin II (ANG-II)-responsive adrenoc ortical autotransplants. VIP significantly increased plasma aldosteron e (ALDO) concentration (PAC) and lowered plasma renin activity (PRA) i n both groups of animals, without affecting plasma levels of ACTH and corticosterone. This treatment caused a marked hypertrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells (without inducing any significant change in the zona-fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant quarters obtained from VIP-infused rats evidenced a notable increase in both their basal and maximally ACTH- or ANG-II-stimulated ALDO secr etion. The simultaneous infusion of rats with VIP-A completely reverse d all these effects of VIP. The infusion with VIP-A alone caused, in s ham-operated rats, a net decrease in PAC, coupled with a rise in PRA, and a marked atrophy of ZG and ZG cells; basal and maximally stimulate d ALDO secretion of dispersed ZG cells was also significantly lowered. Conversely, VIP-A did not evoke any appreciable effect in autotranspl anted rats. These findings suggest that endogenous VIP is specifically involved in the maintenance of the growth and secretory capacity of r at adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to VIP but not to VIP-A infusion, are completely depri ved of chromaffin cells, the hypothesis is advanced that adrenal medul la may be the source of endogenous VIP regulating ZG function.