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 (Delta = -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 (Delta = -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.
Hofman
Cipy
C
The Hypertension Unit, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Francis
Bahaa
B
Rosenthal
Talma
T
Winaver
Joseph
J
Rubinstein
Irit
I
Abassi
Zaid
Z
D000818:Animals; D001794:Blood Pressure; D003300:Copper / Q000172:deficiency; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism*; D006439:Hemodynamics; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply*; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation
D019422:Dietary Sucrose; D019332:Endothelin-1; D003300:Copper