EXPERIMENTAL-HYPERTENSION PRODUCES DIVERSE CHANGES IN THE REGIONAL VASCULAR-RESPONSES TO ENDOTHELIN-1 IN THE RABBIT AND THE RAT

Objective: To examine the effects of hypertension on systemic and regi onal haemodynamic responses to endothelin-1 Design: Comparison of resp onses between age-matched control and hypertensive rabbits (two-kidney , two wrapped), and between spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats. Methods: Arterial pressure, heart rate and blood flow responses to 0.2 nmol/kg intravenous endothelin-1 were meas ured in conscious animals. Blood flow was measured by pulsed ultrasoun d Doppler in the ascending aorta, distal abdominal aorta, left renal a rtery and superior mesenteric artery. Results: Endothelin-1 produced q ualitatively similar effects in the hypertensive and control animals. In the systemic circulation, brief initial vasodilation preceded susta ined vasoconstriction. In the hindlimb, marked vasodilation preceded r elatively minor vasoconstriction, and profound vasoconstriction occurr ed in the renal and mesenteric vascular beds. In the rats but not the rabbits, fleeting vasodilation preceded the renal and mesenteric vasoc onstriction. Significant differences between hypertensive and control animals were: accentuation of the presser effect and heart rate respon ses in hypertensive animals of both species, and accentuation of hindl imb vasodilation in hypertensive rabbits but not SHR; and attenuation of the depressor effect in SHR but not hypertensive rabbits, attenuati on of the mesenteric vasoconstriction in both hypertensive rabbits and rats, and attenuation of renal vasoconstriction in SHR. Conclusions: The increased responses to endothelin-1 of some variables in the hyper tensive animals may involve structural changes in the resistance vesse ls. However, the reduced responses in the mesenteric vasculature of bo th species and the renal vasculature of the SHR are due to some mechan ism other than structural change.