Endothelin receptor function in mesenteric veins from deoxycorticosterone acetate salt-hypertensive rats

Objectives To identify the receptors by which endothelin-1 (ET-1) increases venomotor tone in hypertension. Methods Vascular reactivity to ET-1 and the selective endothelin receptor subtype B (ETB) agonist, sarafotoxin 6c (S6c), was studied in mesenteric blood vessels from deoxycorticosterone acetate (DOCA-salt) hypertensive and normotensive control rats. The diameter of small (less than or equal to 280 mum) mesenteric arteries and veins was monitored in vitro using computer-assisted video microscopy. Contractions of mesenteric arteries (less than or equal to 250 mum diameter) were also studied, using a myograph. ET-1 mRNA levels were measured in mesenteric arteries and veins using real-time RT-PCR techniques. Results ET-1-induced contractions were reduced in arteries of DOCA-salt hypertensive rats compared with those of normotensive control rats; S6c produced negligible contractions in arteries from both groups. ET-1 concentration-responses curves in arteries measured using video microscopy or a myograph were similar. ET-1 and S6c caused veins to contract, and there were no differences between responses to these agonists in tissues from DOCA-salt hypertensive rats or normotensive control rats. Studies using ETA and ETB receptor antagonists indicated that ET-1-induced venoconstriction was mediated by ETA receptors. Potassium chloride concentration-response curves were similar in arteries and veins from normotensive control rats and DOCA-salt hypertensive rats. ET-1 mRNA levels in DOCA-salt hypertensive rat arteries or veins were not different from those in normotensive control rat arteries and veins. Conclusions These data indicate that ET-1 reactivity is maintained in mesenteric veins, but not arteries, in DOCA-salt hypertension. Therefore, the sustained increase in venomotor tone mediated by ETA receptors that is known to occur in vivo in DOCA-salt hypertensive rats is not caused by direct venoconstriction. J Hypertens 20:665-676 (C) 2002 Lippincott Williams Wilkins.