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

SUMMARY 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.