Endothelin mediates a component of the enhanced myogenic responsiveness of arterioles from hypertensive rats.
OBJECTIVE
To determine if the enhanced pressure-induced constriction of arterioles isolated from hypertensive rats is mediated by the endothelium.


METHODS
We utilized isolated, cannulated first-order arterioles (80 to 110 microns, i.d.) from the rat cremaster muscle of spontaneously hypertensive (SHR) and normotensive (WKY) rats. Arteriolar diameter was measured in response to changes in intraluminal pressures as well as various pharmacological agents in the presence and absence of an intact endothelial cell lining.


RESULTS
All arterioles developed intrinsic tone (approximately 74% of passive). Pressure-diameter relationships over a pressure range of 30 to 170 cm H2O demonstrated that the myogenic response of arterioles derived from both WKY and SHR was not dependent upon an intact endothelium. However, at higher pressures (> 170 cm H2O) the ability of the denuded arteriole from the SHR to maintain a constricted diameter was completely abolished. Treatment of arterioles from the SHR having intact endothelium with diclofenac (10(-5) M; 30 min) to inhibit the effect of cyclooxygenase had no effect on the high pressure constriction. In contrast, application of BQ-123 (10(-7) M; 30 min), an ET-A receptor blocker used to inhibit vascular smooth muscle responses to endothelin, completely abolished the arteriolar constriction at higher pressures.


CONCLUSIONS
Therefore, in the hypertensive, arteriolar vasomotor responses to changes in intraluminal pressure is due to at least two mechanisms; one that is intrinsic to vascular smooth muscle (i.e., myogenic) and a second that involves an endothelial cell release of endothelin.
Falcone
J C
JC
Department of Physiology and Biophysics, University of Louisville, KY, USA.
Meininger
G A
GA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D004008:Diclofenac / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016232:Endothelins; D004008:Diclofenac