VASCULAR ALPHA-2-ADRENOCEPTOR FUNCTION IS DECREASED IN RATS WITH CONGESTIVE-HEART-FAILURE

Objective: Vascular alpha-2 adrenoceptor function of rats with congest ive heart failure (CHF) was characterized in both in vivo and in vitro experiments. Methods: CHF was induced in Sprague-Dawley rats by coron ary artery ligation. Sham-operated rats served as normal controls. Pos tjunctional alpha-2 adrenergic responsiveness was assessed in vivo usi ng the pithed rat model and in vitro in organ bath. Vascular alpha-2 a drenoceptor density was studied by receptor binding assay. Results: Fo ur to 6 weeks after this surgical procedure, plasma catecholamines wer e markedly increased in CHF rats. In vivo vascular responses to alpha- 2 adrenoceptor agonists BHT933 and clonidine were significantly decrea sed in CHF rats (P < 0.001). Clonidine elicited dose-dependent respons es in endothelium intact mesenteric arteries in both CHF and sham-oper ated rats. The dose-response curve in CHF was shifted to the right wit h a pD(2) value of 5.5 +/- 0.2 compared with control rats 6.2 +/- 0.2 (P < 0.05). The response to clonidine was selectively blocked by an al pha-2 adrenergic antagonist rauwolscine in both groups. Endothelium de nuded arteries showed an enhanced response to clondine in both CHF and control rats. However, the response to clondine is still decreased in CHF compared to sham-operated rats (P < 0.05). Alpha-2 adrenoreceptor density, as determined by [H-3]yohimbine binding in membrane preparat ions from mesenteric arteries was decreased in CHF compared to sham-op erated rats (B-max 43 +/- 6 vs. 104 +/- 20 fmol/mg protein, P < 0.05). Conclusions: Vascular alpha-2 adrenoceptor function is decreased in r ats with CHF.