Impaired function of endothelial pressure-activated cation channel in salt-sensitive genetic hypertension

Mechanosensitive ion channels have been suggested to act as endothelial mec hanosensors for hemodynamic forces. The present study tested the hypothesis that the pressure activated cation channel (PAC), a novel type of endothel ial mechanosensitive ion channel, is involved in salt sensitivity in the Sa bre rat model of hypertension. Groups of Sabra salt: sensitive (SBH/y) and salt-resistant (SBN/y) rats were loaded with deoxycorticosterone-acetate (D OCA)-salt for 8 wk or were fed a regular diet. Single channel function of P AC in SBH/y and SBN/y rats was investigated in intact endothelium of mesent eric artery using the patch-clamp technique. After DOCA-salt treatment, the SBH/y rats showed a full hypertensive response, whereas (SBN/y) rats were normotensive. Rats of both strains that received a regular diet were normot ensive. In endothelium of both Sabre rats, Ca2+ permeable PAC that was acti vated by positive pipette pressures was identified. Apparent PAC density (p ercentage of patches with PAC activity) was reduced in hypertensive SBJ/y r ats that were loaded with DOCA-salt compared with salt-loaded normotensive SBN/y rats (6 +/- 2% versus 24 +/- 8%, respectively; P < 0.05). In normoten sive SBH/y and SBN/y rats that received a regular diet, PAC density was not altered. Mechanosensitivity and unitary conductance of endothelial PAC wer e similar in both strains under a regular diet as well as salt loading with DOCA-salt. In conclusion, the decreased density of PAC in mesenteric endot helium from hypertensive SBH/y rats indicates an impaired ion channel regul ation. The defective PAC function presumably leads to an impaired mechanose nsitive Ca2+ entry and might contribute to endothelial dysfunction and high BP in this type of salt-sensitive genetic hypertension.