Increased sensitivity of vascular smooth muscle to nitric oxide in dilatedcardiomyopathy of syrian hamsters (Bio TO-2 strain)

We assessed the evolution with time of the responsiveness of three vascular beds in dilated cardiomyopathic hamsters of the Bio TO-2 strain. Eight car diomyopathic hamsters and 8 control hamsters were investigated at 180 and 3 00 days of age. Thoracic aorta and mesenteric and renal artery rings were s tudied in isolated organ baths. Cumulative concentration-response relations to phenylephrine, acetylcholine, sodium nitroprusside, and angiotensin II were established for each ring. Maximum effect (E-max) and concentration in ducing 50% of E-max (EC50) were determined from each concentration-response curve and pD(2) was calculated as -log(EC50). Compared with control hamste rs, in cardiomyopathic hamsters, E-max of phenylephrine was not modified in aorta, whereas it was significantly lower in mesenteric (-6% and -33% at 1 80 and 300 days, respectively) and renal (-17% and -24%) arteries. E-max of acetylcholine was significantly higher in aorta (+57% and +30%), mesenteri c (+42% and +34%), and renal (+168% and +70%) arteries. E-max of sodium nit roprusside was significantly higher in aorta (+26% and +16%) and tended to be higher in mesenteric (+25% and +23%) and renal (+27% and +10%) arteries. E-max of angiotensin II was not modified in aorta and tended to be lower i n mesenteric artery at 300 days. The pD(2) of phenylephrine was significant ly increased in aorta and the pot of sodium nitroprusside was significantly increased in aorta and renal artery. In conclusion, in dilated cardiomyopa thic hamsters, endothelium-dependent and -independent vasodilations are enh anced early, demonstrating increased sensitivity of vascular smooth muscle to nitric oxide. This abnormality may be involved in the decreased responsi veness to phenylephrine and angiotensin II.