Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats

Abstract

In both normally hydrated and volume-expanded rats, there was a biphasic effect of corticotropin-releasing hormone (CRH) (1-10 g, i.v.) on renal function. Within the first hour, CRH caused antidiuresis, antinatriuresis, and antikaliuresis together with reduction in urinary cGMP output that, in the fourth hour, were replaced by diuresis, natriuresis, and kaliuresis accompanied by increased cGMP output. Plasma arginine vasopressin (AVP) concentrations increased significantly within 5 min, reached a peak at 15 min, and declined by 30 min to still-elevated values maintained for 180 min. Changes in plasma atrial natriuretic peptide (ANP) were the mirror image of those of AVP. Plasma ANP levels were correlated with decreased ANP in the left ventricle at 30 min and increased ANP mRNA in the right atrium at 180 min. All urinary changes were reversed by a potent AVP type 2 receptor (V 2R) antagonist. Control 0.9% NaCl injections evoked an immediate increase in blood pressure and heart rate measured by telemetry within 3-5 min. This elevation of blood pressure was markedly inhibited by CRH (5 g). We hypothesize that the effects are mediated by rapid, direct vasodilation induced by CRH that decreases baroreceptor input to the brain stem, leading to a rapid release of AVP that induces the antidiuresis by direct action on the V 2Rs in the kidney. Simultaneously, acting on V 2Rs in the heart, AVP inhibits ANP release and synthesis, resulting in a decrease in renal cGMP output that is responsible for the antinatriuretic and antikaliuretic effects.

Sodium Load Combined with Low Doses of Exogenous Angiotensin II Upregulate Intrarenal Angiotensin II

“…Another event that could explain the antinatriuretic and antikaliuretic effects observed in the Ang 5-Na groups is that circulating Ang II combined with high salt intake stimulate AT1 receptors within the circumventricular organs [29] , increasing vasopressin secretion [30] , which induces antidiuresis by direct action in the kidney. Simultaneously, vasopressin inhibits atrial natriuretic peptide release by the heart, resulting in a decrease in renal cGMP output which is responsible for antinatriuretic and antikaliuretic effects [31] . Alternatively, the augmented Ang II immunoexpression observed in the collecting ducts could exert an antidiuretic effect in response to the hypertonic saline overload, favoring urinary concentration in this segment of the nephron.…”

3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing’s syndrome

“…Following administration of i.v. 21 As the normal ACTH producing cells in the pituitary gland are atrophic in patients with an ACTH producing adenoma, theoretically there may be differential enhancement patterns between the adenoma and normal pituitary after CRH stimulation. 7,8 The oCRH elicits a larger rise than hCRH.…”

“…It has been shown that the endothelium-derived relaxant factor nitric oxide is involved in the vasodilatatory effects of CRH in rats. 21 As the normal ACTH producing cells in the pituitary gland are atrophic in patients with an ACTH producing adenoma, theoretically there may be differential enhancement patterns between the adenoma and normal pituitary after CRH stimulation.…”

The Corticotropin Releasing Factor System in the Kidney: Perspectives for Novel Therapeutic Intervention in Nephrology

“…It was postulated that CRF infusion leads to rapid vasodilatation which decreases baroreceptor stimulation and hence increases AVP release which in turn causes antidiuresis and inhibition of ANP release from the heart. 61 Similar to CRF, urocortin 1 produces also potent arterial and venous vasodilatation 62-64 ( Fig. 1).…”

“…At the same time, CRF appeared to inhibit the expected arterial pressure increase after normal saline infusion. It was postulated that CRF infusion leads to rapid vasodilatation which decreases baroreceptor stimulation and hence increases AVP release which in turn causes antidiuresis and inhibition of ANP release from the heart …”