Impairment of endothelium-dependent dilatation of basilar artery during chronic hypertension.
The goal of this study was to determine whether responses of the basilar artery are altered during chronic hypertension. We measured the diameter of the basilar artery using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine (10 microM) dilated the basilar artery by 25 +/- 4% (means +/- SE) in WKY but by only 2 +/- 2% in SHR. Bradykinin (1.0 microM) dilated the basilar artery by 12 +/- 1% in WKY, but did not alter diameter in SHR (-0.1 +/- 2%). In contrast, nitroglycerin produced similar vasodilatation in WKY and SHR. Next, we examined the possibility that impaired vasodilatation in SHR may be related to the production of a cyclooxygenase constrictor substance. Indomethacin (10 mg/kg iv) did not restore vasodilatation in response to acetylcholine and bradykinin in SHR. Finally, we examined the role of nitric oxide in dilatation of the basilar artery in response to acetylcholine and bradykinin in WKY. NG-Monomethyl-L-arginine (L-NMMA; 1.0 microM) had little effect on baseline diameter but inhibited vasodilation in response to acetylcholine and bradykinin. Vasodilatation in response to nitroglycerin was not altered by L-NMMA. These findings suggest a profound impairment of endothelium-dependent dilatation of the basilar artery during chronic hypertension. In addition, impaired vasodilatation is not related to the production of a cyclooxygenase constrictor substance. Furthermore, dilatation of the basilar artery in WKY in response to acetylcholine and bradykinin appears to be related to the production of nitric oxide or a substance capable of liberating nitric oxide.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin; D007213:Indomethacin