Cytochrome P450 arachidonic acid metabolites modulate renal tubular function.
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Angiotensin II↗
Biomedical subjects
Bruno A Escalante
Publications and source records attributed to Bruno A Escalante.
Does segmental difference in alpha 1-adrenoceptor subtype explain contractile difference in rat abdominal and thoracic aortae?
The cyclooxygenase inhibitor, indomethacin, depresses adrenergic agonist constriction of endothelium-denuded rat abdominal, but not thoracic, aorta. In order to explain this finding, we explored the possibility of segmental differences in the population of alpha 1-adrenoceptor (AR) subtypes. In endothelium-denuded tissues, phenylephrine elicited concentration-dependent contractions in the thoracic and abdominal aortic rings with potencies and maximal effects that, respectively, did not differ significantly (P > .05). Indomethacin (1 x 10(-5) M) inhibited phenylephrine-induced contractions only in abdominal aorta. The subtype-selective alpha 1D-AR antagonist, BMY 7378, was found to antagonize contractions to phenylephrine competitively in abdominal (pA2 8.44) and thoracic (pA2 8.56) aortic rings. These data are consistent with published alpha 1D-AR functional potency and clonal alpha 1D-AR binding affinity. In addition, cumulative concentration-contraction curves for phenylephrine were competitively antagonized in the rat abdominal and thoracic aortae by prazosin, 5-methylurapidil and WB 4101, with pA2 values of 9.39 and 9.61, 7.64 and 7.85, and 9.43 and 9.58, respectively. These compounds with varying degrees of subtype selectivity inhibited contractions of the thoracic and abdominal aortae with affinities consistent with those determined at the alpha 1D-AR subtype. The results of this study suggest that the contraction to phenylephrine of the rat abdominal and thoracic aorta is mediated via the same alpha 1D-AR subtype.
Adrenergic alpha-Agonists↗
Role of cytochrome P-450 arachidonate metabolites in endothelin signaling in rat proximal tubule.
We examined the rat proximal tubule (PT) response to endothelin-1 (ET-1) in terms of 20-hydroxyeicosatetraenoic acid (HETE) dependency. Arachidonic acid (AA) (1 microM) decreased ouabain-sensitive (86)Rb uptake from 2.1 +/- 0.1 to 0.3 +/- 0.08 ng Rb. 10 microg protein(-1). 2 min(-1) (P < 0.05); 20-HETE (1 microM) had similar effects. Dibromododecenoic acid (DBDD) (2 microM), an inhibitor of omega-hydroxylase, abolished the inhibitory action of AA on (86)Rb uptake whereas the PT response to 20-HETE was unaffected. ET-1 at 0.1, 1, 10, and 100 nM reduced (86)Rb uptake from 2.8 +/- 0.3 in control PTs to 2.4 +/- 0.2, 1.7 +/- 0.1, 0.67 +/- 0.08, and 0.1 +/- 0.03 ng Rb. 10 microg protein(-1). 2 min(-1), respectively. DBDD (2 microM) abolished the inhibitory effect of ET-1 on (86)Rb uptake as did BMS182874 (1 microM), an ET(A)-selective receptor antagonist. ET-1 (100 nM) significantly increased PT 20-HETE release by approximately 50%, an effect prevented by DBDD. N(omega)-nitro-L-arginine-methyl ester (L-NAME), given for 4 days to inhibit nitric oxide synthase (NOS), increased arterial pressure from 92 +/- 12 to 140 +/- 8 mmHg and increased endogenous release of 20-HETE from isolated PTs (measured by gas chromatography/mass spectrometry). In L-NAME-treated PTs, but not in control PTs, 0.1 microM AA inhibited ouabain-sensitive (86)Rb uptake by > 40%; the response to AA was attenuated by DBDD. We conclude that, in the PTs, 1) 20-HETE is a second messenger for ET-1 and 2) conversion of AA to 20-HETE is augmented when NOS is inhibited.
Animals↗