Identification of a nonendothelial cell thromboxane-like constrictor response and its interaction with the renin-angiotensin system in the aorta of spontaneously hypertensive rats.
Aortic ring preparations from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with N omega-nitro-L-arginine (NOLA, 10(-4) M). This produced a sustained contraction in preparations from SHR but not WKY rats. A similar contraction in aortic ring preparations from the SHR was produced with methylene blue (10(-5) M) and NG-monomethyl-L-arginine (10(-5) M). The NOLA-induced contraction was reversed with indomethacin (8 x 10(-6) M), ridogrel (10(-5) M) and SQ 29548 (10(-6) M) thus confirming the involvement of thromboxane A2/prostaglandin H2 processes. Subsequent experiments demonstrated that the thromboxane-like contraction was not dependent upon the presence of endothelial cells and occurred in preparations from young, prehypertensive (5 week) and older (17 week) SHRs. The thromboxane-like contraction was markedly suppressed with chronic captopril treatment and reinstated 4 weeks after withdrawal from captopril. The addition of saralasin (10(-6) M) or captopril (10(-6) M) to aortic ring preparations did not suppress the thromboxane-like contractions. The foregoing findings support the presence of a nonendothelial cell thromboxane-like constrictor agent in the aorta of the SHR that is revealed after impairment of nitric oxide production. The activity of the thromboxane-like constrictor process is not tightly linked to prevailing blood pressure, but is reduced with chronic in vivo inhibition of the angiotensin-converting enzyme.
Dyer
S M
SM
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Taylor
D A
DA
Bexis
S
S
Hime
N J
NJ
Frewin
D B
DB
Head
R J
RJ
D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002216:Captopril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine; D010421:Pentanoic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000502:physiology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000502:physiology*; D019323:omega-N-Methylarginine
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010421:Pentanoic Acids; D011725:Pyridines; D013931:Thromboxanes; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; C045749:SQ 29548; D001120:Arginine; D002216:Captopril; D013930:Thromboxane-A Synthase; C060219:ridogrel; D007213:Indomethacin