Role of Prostaglandins in Acetylcholine-Induced Contraction of Aorta From Spontaneously Hypertensive and Wistar-Kyoto Rats

Abstract

Evidence in support of prostaglandin (PG) H 2 as the endothelium-derived contracting factor released in response to acetylcholine in vessels from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) is to a large degree indirect. Therefore, the purpose of the present study was to test the hypothesis that a prostaglandin or prostaglandins other than PGH 2 may serve as the endothelium-derived contracting factor that mediates acetylcholine-induced contraction in these vessels. Acetylcholine-induced contraction of endothelium-intact aorta from 7- to 12-month-old SHR and WKY in the presence of the nitric oxide synthase inhibitor N ω -nitro- l -arginine was abolished by indomethacin and only partially decreased by the thromboxane (Tx) A 2 /PGH 2 receptor antagonist SQ29548. Contraction induced by the TxA 2 /PGH 2 receptor agonist U46619 was abolished by SQ29548. These findings suggest that in endothelium-intact aorta from SHR and WKY, acetylcholine causes the release of a cyclooxygenase product other than PGH 2 that induces contraction independently of TxA 2 /PGH 2 receptor activation. To investigate which prostaglandin or prostaglandins could be responsible for the TxA 2 /PGH 2 receptor–independent component, we challenged endothelium-denuded aorta from SHR and WKY with various prostaglandins in the presence of SQ29548. In SQ29548-treated aorta from 7- to 12-month-old rats, maximal contractions to PGF 2 α , PGE 2 , and carbacyclin (a PGI 2 analogue) were greater than the magnitude of acetylcholine-induced contraction. These findings suggest that PGF 2 α , PGE 2 , and/or PGI 2 could serve as mediators of the TxA 2 receptor–independent component of the acetylcholine-induced contraction. However, in studies with SQ29548-treated aorta from 4- to 6-week-old SHR and WKY (an age at which acetylcholine-induced contraction is known to be absent), maximal contraction to PGF 2 α and PGE 2 was also greater or equivalent to that of SQ29548-treated aorta from 7- to 12-month-old rats, whereas carbacyclin induced negligible contraction. Thus, unlike PGE 2 and PGF 2 α , the age-dependent pattern of contraction induced by carbacyclin closely resembles the pattern induced by acetylcholine. We also measured the levels of PGI 2 released in response to acetylcholine and found that they are sufficient to account for the TxA 2 receptor–independent component of the acetylcholine-induced contraction. Thus, we propose that PGI 2 released in response to acetylcholine may serve as the endothelium-derived contracting factor that elicits the TxA 2 /PGH 2 receptor–independent and -dependent components of the acetylcholine-induced contraction.