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

R. Köhler, R. Kreutz, A. Grundig, L. Rothermund, C. Yagil, Y. Yagil, A. R. Pries, J. Hoyer

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Mechanosensitive ion channels have been suggested to act as endothelial mechanosensors for hemodynamic forces. The present study tested the hypothesis that the pressure-activated cation channel (PAC), a novel type of endothelial mechanosensitive ion channel, is involved in salt sensitivity in the Sabra rat model of hypertension. Groups of Sabra salt-sensitive (SBH/y) and salt-resistant (SBN/y) rats were loaded with deoxycorticosterone-acetate (DOCA)-salt for 8 wk or were fed a regular diet. Single channel function of PAC in SBH/y and SBN/y rats was investigated in intact endothelium of mesenteric 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 normotensive. In endothelium of both Sabra rats, Ca2+ permeable PAC that was activated by positive pipette pressures was identified. Apparent PAC density (percentage of patches with PAC activity) was reduced in hypertensive SBH/y rats that were loaded with DOCA-salt compared with salt-loaded normotensive SBN/y rats (6 ± 2% versus 24 ± 8%, respectively; P < 0.05). In normotensive SBH/y and SBN/y rats that received a regular diet, PAC density was not altered. Mechanosensitivity and unitary conductance of endothelial PAC were 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 endothelium from hypertensive SBH/y rats indicates an impaired ion channel regulation. The defective PAC function presumably leads to an impaired mechanosensitive Ca2+ entry and might contribute to endothelial dysfunction and high BP in this type of salt-sensitive genetic hypertension.

Original languageEnglish
Pages (from-to)1624-1629
Number of pages6
JournalJournal of the American Society of Nephrology : JASN
Volume12
Issue number8
StatePublished - 4 Aug 2001
Externally publishedYes

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