CORONARY VASCULAR-RESPONSE TO ENDOTHELIN IN ISOLATED PERFUSED HEARTS OF SPONTANEOUSLY HYPERTENSIVE RATS

1. The coronary vasoconstrictive response to endothelin (ET-1) was evaluated using the isolated perfused hearts of 15 week old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Endothelin produced marked increases in perfusion pressure (PP) in both SHR and WKY. The effects of ET-1 were more potent than those of acetylcholine, vasopressin and angiotensin II. The vascular response to ET-1, expressed as the increase in PP, was greater in SHR than in WKY. 2. Nicardipine (10(-8) mol/L) shifted the concentration-PP response curve for ET-1 to the right. The extent of the rightward shift was greater in SHR than in WKY. Additionally in SHR, Bay K-8644 elicited a dose-dependent increase in PP, the effect being more potent than that in WKY. 3. The increased response of the coronary vasculature to ET-1 was observed after 15 weeks of age but not at 6 weeks, indicating that enhancement of the response develops with ageing in SHR. 4. Enhancement of the vascular response to ET-1 in SHR was prevented by chronic (10 weeks) treatment with enalapril (10 mg/kg per day), but not by hydralazine (30 mg/kg per day). 5. These results indicate that the coronary vascular response to ET-1 increases with age in SHR. The mechanism of the enhanced response may involve the activation of dihydropyridine-sensitive Ca2+ channels, however, this type of mechanism may also be modulated at least in part by the renin-angiotensin system.