Submitted on September 1, 2006
Accepted on December 20, 2006
NITRIC OXIDE PATHWAY COUNTERACTS ENHANCED CONTRACTION TO MEMBRANE DEPOLARIZATION IN AORTIC RINGS OF RATS ON HIGH SODIUM DIET
Magali Cordaillat1, Aurélie Fort2, Anne Virsolvy3, Jean-Luc Elghozi4, Sylvain JM RICHARD3, and Bernard F Jover5*
1 Groupe Rein & Hypertension, University Montpellier I, Montpellier, France; U652, INSERM, Paris, France
2 Physiopathologie Cardiovasculaire, INSERM U-637, Montpellier Cédex 05, France
3 Physiopathologie Cardiovasculaire, INSERM U-637, Montpellier cédex 05, France
4 U652, INSERM, Paris, France
5 Groupe Rein & Hypertension, University Montpellier I, Montpellier, France
* To whom correspondence should be addressed. E-mail: jover{at}montp.inserm.fr.
Vascular smooth muscle cell contraction and endothelium-dependent relaxation was evaluated in aortic rings isolated from Sprague-Dawley rats fed normal or high sodium (NS 0.8%, HS 8% NaCl) diet since weaning to the age of 5 months. Arterial pressure was 140±6 and 145±6 mmHg in NS and HS rats, respectively. In endothelium-denuded rings, the response to PE was not modified by the sodium diet while that of depolarizing agent KCl and intracellular calcium releasing agent caffeine increased in the HS group. When endothelium was preserved, PE-evoked contraction was reduced in both NS and HS group, the contraction being yet lower in the HS group. This effect was partially obliterated by the addition of L-NAME, independently of the sodium diet. Relaxation to Ach in intact rings and to SNP and 8-BrcGMP in absence of endothelium was enhanced in rings isolated from HS rats. In addition, the dose-response curve to 8-BrcGMP was shifted to the right in presence of iberiotoxin, an inhibitor of large conductance, voltage-dependent, and calcium-sensitive potassium channel (BKCa). However, the shift was more marked in rings from HS rats. The present results provide evidence that the response of vascular smooth muscle cell to NO/cGMP related compounds is increased in HS rings and associated with a greater activation of the repolarizing BKCa channels. Such changes might counterbalance the enhanced contractile response to membrane depolarization, and thus participate in the maintenance of arterial pressure in the present model of early and long-term high sodium feeding in rats.
