Endothelium‐dependent contractions in the carotid artery of young adult spontaneously hypertensive rats are mediated by cyclooxygenase and markedly augmented by nitric oxide inhibition

We have recently shown that ACh‐stimulated vasomotor activity in isolated PE‐precontracted common carotid artery (CCA) rings from young adult spontaneously hypertensive rats (SHR) involves a dose‐dependent relaxation phase from −9 to −7 LogM followed by a ‘re’‐contraction phase through to −4 LogM, whereas in normotensive Wistar Kyoto rats (WKY) only a robust relaxation phase existed. The objective of this study was to test the hypothesis that [ACh] >−7 LogM stimulates contractions in quiescent CCA from SHR but not WKY. Reference KCl contractions in CCA were similar between strains and across all drug conditions (0.9−1.0g). [ACh] from −9 to −4 did not elicit vasomotor activity in WKY CCA, nor did [ACh] elicit vasomotor activity in SHR CCA from −9 to −7; however, [ACh] >−7 stimulated a dose‐dependent contraction in SHR CCA reaching a plateau at −4 (0.16±0.03g). Endothelium denudation completely abolished these ACh‐stimulated contractions as did cyclooxygenase (COX) inhibition, whereas blocking endothelial nitric oxide (NO) synthase markedly increased the amplitude (0.61±0.08g) but not the threshold or sensitivity of the contractile response. These data demonstrate that only [ACh] >−7 LogM can stimulate contractions in CCA from young adult SHR (but not WKY) that are endothelium‐dependent, COX‐mediated, and powerfully modulated by the availability of NO. Research Support: HSFO and NSERC