Increased inward rectifier K + current of coronary artery smooth muscle cells in spontaneously hypertensive rats; partial compensation of the attenuated endothelium‐dependent relaxation via Ca 2+ ‐activated K + channels

Endothelium‐dependent vasorelaxation is partly mediated by small‐conductance ( SK 3) and intermediate‐conductance Ca 2+ ‐activated K + channels ( SK 4) in the endothelium that results in endothelium‐dependent hyperpolarization ( EDH ). Apart from the electrical propagation through myoendothelial gap junctions, the K + released from the endothelium facilitates EDH by increasing inward rectifier K + channel (Kir) conductance in smooth muscle cells. The EDH ‐dependent relaxation of coronary artery ( CA ) and Kir current in smooth muscle cells ( CASMC s) of hypertensive animals are poorly understood despite the critical role of coronary flow in the hypertrophic heart. In spontaneously hypertensive ( SHR ) and control ( WKY ) rats, we found attenuation of the CA relaxation by activators of SK 3 and SK 4 ( NS 309 and 1‐ EBIO ) in SHR . In isolated CASMC s, whole‐cell patch‐clamp study revealed larger I Kir in SHR than WKY , whereas the myocytes of skeletal and cerebral arteries showed smaller I Kir in SHR than WKY . While the treatment with I Kir inhibitor (0.1 mmol/L Ba 2+ ) alone did not affect the WKY ‐ CA , the SHR ‐ CA showed significant contractile response, suggesting relaxing influence of the higher I K ir in the CASMC s of SHR . Furthermore, the attenuation of NS 309‐induced relaxation of CA by the combined treatment with 0.1 mmol/L Ba 2+ was more prominent in SHR than WKY . Our study firstly shows a distinct increase of I K ir in the CASMC s of SHR , which could partly compensate for the attenuated relaxation via endothelial SK 3 and SK 4.