Previous studies, by this group and others, have shown that vasoactive inte
stinal peptide (VIP) stimulates aldosterone secretion, and that the actions
of VIP on aldosterone secretion by the rat adrenal cortex are blocked by b
eta adrenergic antagonists, suggesting that VIP may act by the local releas
e of catecholamines. The present studies were designed to test this hypothe
sis further, by measuring catecholamine release by adrenal capsular tissue
in response to VIP stimulation.
Using intact capsular tissue it was found that VIP caused a dose-dependent
increase in aldosterone secretion, with a concomitant increase in both adre
naline and noradrenaline release. The effects of VIP on aldosterone secreti
on were inhibited by atenolol, a beta(1) adrenergic antagonist, but not by
ICI-118,551, a beta(2) adrenergic antagonist. Binding studies were carried
out to investigate VIP receptors. It was found that adrenal zona glomerulos
a tissue from control rats contained specific VIP binding sites (B-max 853
+/- 101 fmol/mg protein; K-d 2.26 +/- 0.45 nmol/l). VIP binding was not dis
placed by ACTH, angiotensin II or by either of the beta adrenergic antagoni
sts.
The response to VIP in adrenals obtained from rats fed :I low sodium diet w
as also investigated. Previous studies :have found that adrenals front anim
als on a low sodium diet exhibit increased responsiveness to VIP. Specific
VIP binding sites were identified, although the concentration or affinity o
f binding sites in the low sodium group was not significantly different fro
m the controls. In the low sodium group VIP was found to increase catechola
mine release to the same extent as in the control group, however, in contra
st to the control group, the adrenal response to VIP was not altered by adr
energic antagonists in the low sodium group.
These data provide strong support for the hypothesis that VIP acts by the l
ocal release of catecholamines in adrenal zona glomerulosa tissue in normal
animals. It does not appear that VIP acts through the same mechanism in an
imals maintained on a low sodium diet. The mechanism by which VIP stimulate
s aldosterone in this group remains to be determined.