Renin‐angiotensin Mediation of Adrenal Catecholamine Secretion Induced by Hypoglycaemia in the Cat

Abstract

The mechanism involved in catecholamine (CA) release from the cat adrenal gland in response to insulin hypoglycaemia was studied. In intact cats, hypoglycaemia induced an 11 fold increase in adrenomedullary CA secretion. Acute bilateral nephrectomy nearly abolished the increased CA release from the adrenal gland during hypoglycaemia. Infusion of Sar1‐Ileu8‐Angiotensin II (AII), a competitive AII antagonist, suppressed the adrenomedullary response to the insulin‐induced hypoglycaemia. After termination of the antagonist infusion, CA secretion from the adrenal medulla increased rapidly, reaching the same level as in insulin‐treated cats. Infusion of rabbit anti‐angiotensin I antibodies suppressed CA release from the adrenal gland of hypoglycaemic cats. This effect was more prolonged than that of Sar1‐Ileu8‐AII. These results indicate that CA release from the adrenal medulla of the cat in response to insulin‐induced hypoglycaemia, is mediated through the renal reninangiotensin system. Since hypoglycaemia causes sympathetic stimulation through a central mechanism, angiotensin may act through the central nervous system.

Brain angiotensin receptors and sympathoadrenal regulation during insulin-induced hypoglycemia

“…Thus exogenous angiotensin II stimulates Epi secre-tion in vivo (24), and high concentrations of angiotensin II stimulate Epi release from isolated perfused adrenals (33). Furthermore, nonselective angiotensin II receptor blockade with [Sar,Ile]-angiotensin abolishes adrenomedullary catecholamine release during insulin-induced hypoglycemia (4). We showed that the increase in plasma Epi concentration during insulininduced hypoglycemia is unaltered by selective AT 1receptor blockade in both rats and humans (34,35).…”

Captopril does not affect reflex increases in adrenal or lumbar sympathetic nerve activity to hypoglycemia in rats

“…As an additional mechanism, ACE inhibitors may impair the release of epinephrine during hypoglycemia, which is considered one of the most important counterregulatory hormones during periods of severe depressions in blood glucose. In favor of this, hypoglycemia-induced elevations in epinephrine were inhibited by anti-angiotensin I (ANGI) antibodies [8], angiotensin II (ANGII) antagonism with saralasin [8,9], inhibition of ACE [8][9][10][11], and inhibition of AT 1 and AT 2 receptors [11,12] in most but not all [13] studies.…”

Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

“…Accordingly, nephrectomy or treatment with a non-selective Ang II receptor antagonist nearly abrogates catecholamine release from cat adrenal medulla in response to the stress of insulin-induced hypoglycemia (Bumpus, et al 1980). Ang II also induces catecholamine biosynthesis by elevating gene expression of the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) (Stachowiak, et al 1990b).…”