Enhanced Ca2+-induced contractions and attenuated α-adrenoceptor responses in resistance arteries from rats with congestive heart failure

Aim: The aim of the present study was to examine the role of Ca2+-mediated contractile responses in isolated mesenteric resistance arteries from rats with congestive heart failure (CHF). Methods: Heart failure was induced by ligation of the left coronary artery. Rats exposed to the same surgical procedure except ligation served as controls (Sham). The following experiments were conducted: (1) passive increase in radial stretch (the length-tension relationship) in Ca2+-free and in depolarizing high K+-solution; (2) the contractile responses to external application of Ca2+ and high K+-solutions in the presence of nifedipine and phentolamine; and (3) a histological evaluation of CHF and Sham vessels. Results: The length-tension induced response in Ca2+-free buffer solution was significantly lower in arteries from CHF rats, starting at a very low tension (0.9 +/- 0.2 mN/mm for heart failure and 1.7 +/- 0.2 mN/mm for Sham). This difference, but at a higher degree of stretch, was also present in K+-activated vessels. The external application of Ca2+ in K+-depolarized vascular segments in the presence of phentolamine (1 muM) induced an enhanced contractile response in arteries from CHF rats compared with Sham (4.8 +/- 0.3 mN/mm and 3.6 +/- 0.6 mN/mm, respectively, P = 0.059). In the absence of phentolamine the reverse response was found (4.0 +/- 0.4 mN/mm and 5.7 +/- 0.3 mN/mm for CHF vs. Sham respectively, P = 0.035). Application of increasing concentrations of K+-solution induced a stronger contractile response in Sham compared with CHF arteries (Sham 4.9 +/- 0.4 and heart failure 4.0 +/- 0.3, P = 0.04). Microscopic examination of vessels yielded no difference in gross morphology, media thickness or wall to lumen ratio between CHF and Sham arteries. Conclusion: The results indicate an attenuation of alpha -adrenoceptors and a difference of Ca2+-mediated vascular contractility in resistance arteries of congestive heart failure rats. (C) 2001 European Society of Cardiology. All rights reserved.