ROLE OF PROSTAGLANDINS IN ACETYLCHOLINE-INDUCED CONTRACTION OF AORTA FROM SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

Evidence in support of prostaglandin (PG) H-2 as the endothelium-deriv ed contracting factor released in response to ace tylcholine in vessel s from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto ra ts (WKY) is to a large degree indirect. Therefore, the purpose of thr present study was to test the hypothesis that a prostaglandin or prost aglandins other than PGH(2), may serve as the endothelium-derived cont racting factor that mediates acetylcholine-induced contraction in thes e vessels. Acetylcholine-induced contraction of endothelium-intact aor ta from 7- to 12-month-old SHR and WKY in the presence of the nitric o xide synthase inhibitor N-w-nitro-L-arginine was abolished by indometh acin 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 U46519 was abolished by SQ29548. These findings sugge st that in endothelium-intact aorta from SHR and WKY, acetylcholine ca uses the release of a cyclooxygenase product other than PGH(2) that in duces contraction independently of TxA(2)/PGH(2) receptor activation. To investigate which prostaglandin or prostaglandins could be responsi ble for the TxA(2)/PGH(2) receptor-independent component, we challenge d endothelium-denuded aorta from SHR and WKY with various prostaglandi ns in the presence of SQ29548. In SQ29548-treated aorta from 7- to 12- month-old rats, maximal contractions to PGF(2 alpha), PGE(2), and carb acyclin (a PGI(2) analogue) were greater than the magnitude of acetylc holine-induced contraction. These findings suggest that PGF(2 alpha,) PGE(2), and/or PGI(2) could serve as mediators of the TxA(2) receptor- independent component of the acetylcholine-induced contraction. Howeve r, 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 alpha) and PGE(2) was also grea ter or equivalent to that of SQ29548-treated aorta from 7- to 12-month -old rats, whereas carbacyclin induced negligible contraction Thus, un like PGE(2) and PGF(2 alpha), the age-dependent pattern of contraction induced by carbacyclin closely resembles the pattern induced by acety lcholine. We also measured the levels of PGI, released in response to acetylcholine and found that they are sufficient to account for the Tx A(2) receptor-independent component of the acetylcholine-induced contr action Thus, we propose that PGI(2) released in response to acetylchol ine may serve as the endothelium-derived contracting Factor that elici ts the TxA(2)/PGH(2) receptor-independent and -dependent components of the acetylcholine-induced contraction.