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

• Published in: Journal of the American Society of Nephrology Vol. 12; no. 8; pp. 1624 - 1629
• Main Authors: KÖHLER, Ralf, KREUTZ, Reinhold, GRUNDIG, Alexander, ROTHERMUND, Lars, YAGIL, Chana, YAGIL, Yoram, PRIES, Axel R, HOYER, Joachim
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.08.2001
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cations - metabolism; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Desoxycorticosterone - pharmacology; Drug Resistance; Endothelium, Vascular - physiopathology; Hypertension - genetics; Hypertension - physiopathology; Ion Channels - physiology; Medical sciences; Mesenteric Arteries - physiopathology; Patch-Clamp Techniques; Pressure; Rats; Rats, Inbred Strains; Sodium Chloride - pharmacology; Hypertension; Kidney disease; Vertebrata; Urinary system disease; Mammalia; Renal function; Rat; Animal; Rodentia; Cardiovascular disease; Complication; Exploration
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.V1281624

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, Ca(2+) 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 Ca(2+) entry and might contribute to endothelial dysfunction and high BP in this type of salt-sensitive genetic hypertension.