Premium
Endothelium‐dependent contractions in the carotid artery of young adult spontaneously hypertensive rats are mediated by cyclooxygenase and markedly augmented by nitric oxide inhibition
Author(s) -
Denniss Steven G,
Rush James WE
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1154.6
Subject(s) - vasomotor , nitric oxide , contraction (grammar) , endocrinology , vasodilation , medicine , chemistry , endothelium , cyclooxygenase , nitric oxide synthase , enzyme , biochemistry
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