© 2001 European Society of Cardiology
Enhanced Ca2+ -induced contractions and attenuated
-adrenoceptor responses in resistance arteries from rats with congestive heart failure
a Department of Internal Medicine, Lund University Lund, Sweden
b Department of Clinical Pharmacology, Gothenburg University Gothenburg, Sweden
* Corresponding author. Tel.: +46-46-171237; fax +46-46-184792. E-mail address: lars.edvinsson{at}med.lu.se (L. Edvinsson).
| Abstract |
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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 µM) 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
-adrenoceptors and a difference of Ca2+ -mediated vascular contractility in resistance arteries of congestive heart failure rats.
Key Words: Ca2+ Congestive heart failure
-Adrenoceptors
Received November 12, 1999; Revised May 11, 2000; Accepted June 8, 2000