Role of prostaglandin H2-thromboxane A2 in responses of cerebral arterioles during chronic hypertension.
The goal of this study was to determine the role of prostaglandin H2-thromboxane A2 (PGH2-TxA2) in altered responses of cerebral arterioles during chronic hypertension. Diameter of pial arterioles was measured during suffusion with ADP, acetylcholine, and nitroglycerin using intravital microscopy in Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHR) (8-10 mo old). ADP (100 microM) increased pial arteriolar diameter by 21 +/- 3% (means +/- SE) in WKY and only by 7 +/- 3% in SHR. Acetylcholine (10 microM) increased diameter 10 +/- 2% in WKY and, in contrast, reduced diameter 7 +/- 3% in SHR. Nitroglycerin produced similar vasodilatation in WKY and SHR. We then examined whether impaired dilatation of cerebral arterioles in SHR to ADP and acetylcholine may be related to activation of the PGH2-TxA2 receptor. SQ 29548, a specific PGH2-TxA2 receptor antagonist, restored vasodilatation in response to ADP in SHR toward that observed in WKY and reversed vasoconstriction to vasodilatation in response to acetylcholine in SHR. SQ 29548 did not alter responses in WKY. Thus these findings suggest that impaired responses of cerebral arterioles to ADP and acetylcholine during chronic hypertension may be related to the activation of the PGH2-TxA2 receptor.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha 68198.
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001921:Brain / Q000098:blood supply*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002908:Chronic Disease; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007093:Imidazoles; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D014665:Vasodilator Agents; C039242:dazmegrel; D044262:Prostaglandin H2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C045749:SQ 29548; D005996:Nitroglycerin; D000109:Acetylcholine