Effects of KRN2391-induced hypotension on the endocrine system and carbohydrate metabolism in halothane-anesthetized dogs

Abstract

Purpose: The hemodynamic profiles of KRN2391-induced hypotension have been reported to be a hyperdynamic state. However, the endocrine effects of KRN2391-induced hypotension remain to be elucidated. We investigated the endocrine and metabolic effects of KRN2391-induced hypotension on the plasma concentrations of catecholamines, aldosterone, cortisol, glucose, and lactic acid and on plasma renin activity.

Methods: Eight dogs were anesthetized with 087% halothane in oxygen. After a baseline period, mean arterial pressure (MAP) was lowered to 60 mmHg for 60min by the infusion of KRN2391.

Results: KRN2391-induced hypotension resulted in a 50% decrease (P<0.01) in MAP due to a 80% reduction (P<0.01) in systemic vascular resistance associated with a 224% increase (P<0.01) in cardiac index. Plasma norepinephrine concentrations increased (P<0.01) after 60 min of hypotension. Plasma epinephrine concentrations and plasma renin activity both increased (P<0.05) during the hypotensive period. Plasma aldosterone concentrations remained unchanged during the hypotensive period, but then increased (P<0.05) after termination of KRN2391. Plasma cortisol concentrations remained unchanged throughout the observation period. Plasma glucose concentrations increased (P<0.01) during the hypotensive period. Plasma lactic acid concentrations increased (P<0.01) throughout the observation period.

Conclusion: KRN2391-induced hypotension activates the sympathetic nervous system and consequently may modulate the renin-angiotensin-aldosterone axis and carbohydrate metabolism.

Keywords: Carbohydrate metabolism; Catecholamines; Induced hypotension; KRN2391 (potassium channel opener); Renin-angiotensin-aldosterone axis.