Effects of indomethacin on prostanoid synthesis and vasomotor responsiveness in endothelium-denuded abdominal and thoracic aortas of Wistar rats

Abstract

In endothelium-denuded abdominal (but not thoracic) aortas of rats, the nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed contractions evoked by α-adrenergic agonists hypothetically mediated by prostanoids. We aimed to identify these non-endothelial-derived contractile prostanoids released by α-adrenergic receptors activation. Endothelium-denuded abdominal and thoracic aortas of Wistar rats were used for biochemical and functional analyses. Western blot analysis showed that COX-1 and COX-2 protein levels were respectively equivalent in endothelium-denuded abdominal and thoracic aortas. Enzyme immunoassay data supported direct evidence of phenylephrine-stimulated release of prostanoids (PGI, PGE, and PGF) by thoracic and abdominal aortas without endothelium, and their almost complete inhibition by 1 μM indomethacin. Isometric force measurements established that 10 μM indomethacin-but no lower concentrations-inhibited the contractions evoked by phenylephrine in endothelium-denuded abdominal aorta. In this preparation, 10 μM indomethacin also depressed the contractions provoked by angiotensin II and high K (80 mM). In fact, indomethacin (up to 1 mM) caused concentration-dependent reductions in all abovementioned contractile responses. In endothelium-denuded thoracic aortas, however, only 1 mM indomethacin significantly depressed the contractile activity stimulated by either phenylephrine, angiotensin II, or high K. Hence, there was a clear quantitative difference in response to indomethacin between abdominal and thoracic aortas without endothelium. Altogether, the results indicate that prostanoids induced by phenylephrine in abdominal and thoracic aortas were derived from non-endothelial COX-mediated metabolism; notably, the decrease in prostanoid synthesis could not account for the inhibition of vasoconstrictor responses by indomethacin: Through COX-independent actions, indomethacin inhibited aortic smooth muscle contractility.

Adjuvant-induced arthritis promotes vascular hyporesponsiveness to phenylephrine through a nitric oxide-related mechanism

“…It is true that the difference in response between control and AIA animals was smaller in the presence of indomethacin. However, this was due to an expected COX-independent reduction in contractile responses to phenylephrine in the aortas obtained of control animals (27), but without a noticeable change in the pattern of these responses in the AIA animals. 1).…”

Effects of Indomethacin on the Norepinephrine-Induced Contraction in Vascular Smooth Muscle during Different Stages of the Estrous Cycle

“…It has been shown that indomethacin reduced the vascular response to αadrenoceptor agonists in the endothelium-denuded aorta of rat, which could be due to the prevention of vasoconstrictor PGs formation in smooth muscles of aorta by COX-2. (Lopez et al, 2017). Since indomethacin inhibits the release of PGs, it is possible to speculate that the availability of PGs may influence the contractile responses (Jaimes et al, 2019).…”

Sepse experimental aumenta a ação anti-contrátil do tecido adiposo perivascular em aortas de ratos

“…Os prostanóides também estão intimamente relacionados com a hiporresponsividade vascular provocada pela sepse, uma vez que são importantes moduladores do tônus vascular tanto em condições fisiológicas, como fisiopatológicas (Lopez et al, 2017). No presente estudo, observamos que ao utilizar indometacina e RO1138452, ocorreu a reversão do aumento da ação anti-contrátil do PVAT observado durante a sepse.…”