The pressure-activated cation channel (PAC), a novel type of mechanosensitive channel, has been suggested to act as a mechanosensor in aortic endothelium. In experimental hypertension, PAC function was up-regulated in the established phase of high blood pressure. This association of altered PAC function and elevated arterial pressure suggests that PAC function is regulated by alterations in blood pressure. In the present study, we electrophysiologically investigated PAC function in intact endothelium of aorta (EA) and mesenteric artery (EMA) from stroke-prone spontaneously hypertensive rats (SHRSP), SHRSP after 4 weeks of treatment with quinaprilat (10 mg/kg/day), and normotensive Wistar-Kyoto (WKY) rats. In untreated SHRSP and WKY rats, systolic blood pressure (SBP) was 201 ± 3 mm Hg and 142 ± 3 mm Hg, respectively. In quinaprilat-treated SHRSP, SBP was lowered to 135 ± 5 mm Hg. Apparent PAC density (percentage of patches with PAC activity) in EA of untreated SHRSP (63.7% ± 7.3%) was 2.4-fold higher than in WKY rats (26.0% ± 5.0%). In contrast, no significant PAC up-regulation was detected in EMA of SHRSP (15.7% ± 4.2%) compared with WKY rats (12.0% ± 3.9%). In EA of quinaprilattreated normotensive SHRSP, PAC density (27.1% ± 5.2%) was lowered to levels found in normotensive WKY rats. Unitary conductance and pressure sensitivity of PAC were not altered in either hypertensive or normotensive rats. Taken together, hypertension-induced increases of endothelial PAC density can be completely reversed by antihypertensive therapy. The PAC up-regulation in EA was interpreted as a compensatory mechanism to enhance Ca 2+ -influx and subsequently the synthesis of vasodilatory factors. This mechanism is missing in EMA of SHRSP, which might contribute to high blood pressure in this rat model of severe genetic hypertension. © 2001 American Journal of Hypertension, Ltd.
Köhler, R., Grundig, A., Brakemeier, S., Rothermund, L., Distler, A., Kreutz, R., & Hoyer, J. (2001). Regulation of pressure-activated channel in intact vascular endothelium of stroke-prone spontaneously hypertensive rats. American Journal of Hypertension, 14(7 I), 716–721. https://doi.org/10.1016/S0895-7061(01)01306-1