Background:

Voltage-gated potassium (K⁺) channels encoded by KCNQ genes (Kv7 channels) are functionally present in vascular and non-vascular smooth muscle cells (Jepps et al., 2012). Recently, Kv7 channels have been attributed to β-adrenoceptor mediated vasodilatation (Chadha et al., 2012). Also, in hypertension the functional impact of Kv7 channels is dramatically attenuated due to a down-regulation of the Kv7.4 protein (Jepps et al., 2011). The aim of this study was to determine whether Kv7 channels may also to contribute cGMP-mediated vasorelaxations.

Methods and Results:

Isometric tension recordings were performed on segments of thoracic aorta from normotensive Wistar rats and spontaneously hypertensive rats (SHRs). Sodium nitroprusside (SNP) and C-type natriuretic peptide (CNP) were applied to preconstricted aorta segments from normotensive rats causing a dose-dependent relaxation. The vessels were then washed and the SNP and CNP dose-response curves were repeated in the presence of either the Kv7 blocker Linopirdine (10 µM) or the vehicle control (DMSO). In the presence of Linopirdine the CNP relaxation was dramatically attenuated, however, the SNP relaxation was not effected compared to their respective DMSO controls. Also, the ability CNP to relax precontracted vessel segments from hypertensive rats was considerably impaired in tissues isolated from SHRs, however, SNP was equally effective in both normotensive and hypertensive vessels.

Conclusions:

Kv7 channels may contribute to CNP-mediated relaxations, acting through receptor-activated guanylyl cyclase, but not SNP-mediated relaxations.

References:

Jepps et al. (2011) Circulation, 124:602-11; Chadha et al. (2012) Hypertension, 59:877-84; Jepps et al. (2012) Br. J. Pharmacol., doi: 10.1111/j.1476-5381.2012.02133.x.