Effects of endothelin-1 on systemic and renal hemodynamics in hypertensive-diabetic rats (CRDH), diabetic rats (CDR), and hypertensive rats (SHR)

The Cohen-Rosenthal diabetic hypertensive rat is a unique animal model in which genetic hypertension and diabetes developed after crossbreeding of a sensitive substrain of Cohen diabetic rats and spontaneously hypertensive rats (SHR) and feeding them a copper-poor sucrose diet. This study examined the acute effects of endothelin-1 on the systemic and renal hemodynamics in Cohen-Rosenthal diabetic hypertensive rats, Cohen diabetic rats and spontaneously hypertensive rats. Intravenous injection of endothelin-1 (1.0 nmol/kg) into anesthetized SHR resulted in a significant immediate depressor response in mean arterial pressure [from 165 ± 3 mmHg to 124 ± 12 mmHg (P < 0.0001)] followed by a minor hypertensive phase (mean arterial pressure increased to 170 ± 2 mmHg). Simultaneously, the administration of endothelin-1 caused a significant decrease in renal blood flow from 5.8 ± 0.9 mL/minute to 3.2 ± 0.5 mL/minute (P = 0.026). These responses were blunted in Cohen-Rosenthal diabetic hypertensive rats and Cohen diabetic rats. Analysis of intrarenal blood flow by laser-Doppler in Cohen-Rosenthal diabetic hypertensive rats revealed that endothelin-1 injection caused a decrease in cortical blood flow (Δ = -12 ± 2.9%). However, in contrast to its well known renal medullary vasodilatory effect, endothelin-1 produced a significant decline in the medulla blood flow (Δ = -17.5 ± 3.4%) (P = 0.0125). These findings suggest that Cohen diabetic rats and Cohen-Rosenthal diabetic hypertensive rats have reduced sensitivity to the vascular and renal action of endothelin-1. Furthermore, in the Cohen-Rosenthal diabetic hypertensive rats the expected endothelin-1-induced medullary vasodilation was abolished and even reversed into prolonged vasoconstrictor response.