Altered vascular reactivity and KATP channel currents in vascular smooth muscle cells from deoxycorticosterone acetate (DOCA)-salt hypertensive rats

This study was designed to evaluate the contribution of ATP-dependent potassium (K-ATP) channels to the changes in vascular reactivity and spontaneous tone observed in vessels isolated from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phenylephrine preconstricted aortic rings, cromakalim induced concentration-dependent, glibenclamide-sensitive relaxation. The concentration response curve to cromakalim was shifted to the right in DOCA-salt hypertensive rats (EC50: 0.850 +/- 0.100 muM) compared with SHAM-normotensive rats (0.108 +/- 0.005 muM), and the maximum relaxation (E-max) evoked by cromakalim was significantly lower in aortic rings from the DOCA group (68 +/- 2%) compared with the SHAM group (108 +/- 5%). The results were similar in endothelium-denuded rings. Spontaneous tone was observed in aortic rings (5 g preload) from DOCA-salt but not SHAM rats. Cromakalim abolished spontaneous tone and the effect was blocked by glibencamide. In whole cell patch clamp studies, increasing extracellular K+ concentrations from 5.4 to 140 mM and the administration of cromakalim evoked dramatic increases in K-ATP channel currents in aortic cells isolated from SHAM rats. In contrast, in aortic cells from DOCA-salt hypertensive rats, K-ATP channel currents were either absent or weak in response to challenges by elevated extracellular K+ and by cromakalim. These findings suggest that the function of K-ATP channels is impaired in smooth muscle cells from aorta of DOCA-salt hypertensive rats, which may contribute to the impaired vasodilatation and spontaneous tone observed in these rats.