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B Escalante

Publications and source records attributed to B Escalante.

47 records · Page 3Linked to original sources
PubMed1990

Cytochrome P450-dependent arachidonic acid metabolites, 19- and 20-hydroxyeicosatetraenoic acids, enhance sodium-potassium ATPase activity in vascular smooth muscle.

Several cytochrome P450-dependent arachidonic acid metabolites have been shown to affect Na+,K(+)-ATPase activity. In the present study, we tested the effect of omega- and omega - 1-hydroxylated products, i.e., 19- and 20-hydroxyeicosatetraenoic acids (19- and 20-HETE), on the K-induced relaxation in rat aortic rings. 19-HETE and 20-HETE increased the magnitude of the potassium-induced relaxation in a dose-dependent fashion (10(-7)-10(-5) M). The inhibitory effect of ouabain on the potassium-induced relaxation was reversed by both 19- and 20-HETE. In addition, indomethacin fully inhibited the stimulatory effect of 19- and 20-HETE on relaxation induced by potassium. Vascular ouabain-sensitive 86Rb uptake was also increased by 19- and 20-HETE. These observations suggest that 19- and 20-HETE stimulate vascular Na+,K(+)-ATPase via their conversion by cyclooxygenase to prostaglandin-like material.

Analysis of Variance↗
PubMed1990

Effect of heme arginate administration on blood pressure in spontaneously hypertensive rats.

Cytochrome P450 content and activities are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared with those of normotensive, Wistar-Kyoto (WKY), control rats during the period of rapid elevation of blood pressure. We studied the effect of heme arginate, a potent inducer of heme oxygenase (EC 1.14.99.3), on microsomal cytochrome P450 levels and activities and blood pressure in SHR at 7 wk of age. Administration of heme arginate (15 mg/kg body weight for 4 d) resulted in a marked decrease in blood pressure from 156.3 +/- 4.7 to 129.8 +/- 4.5 mm Hg (P less than 0.001), whereas blood pressure in SHR receiving the vehicle control was not affected. The blood pressure of age-matched WKY was not affected by heme arginate. Heme oxygenase activity increased in both hepatic and renal microsomes of SHR and WKY by two- to four-fold after treatment with heme arginate. Maximal increase of heme oxygenase mRNA occurred 5-7 h after the last injection of heme arginate and returned to control levels after 24 h. The increase in heme oxygenase activity was associated with a parallel decrease in cytochrome P450 content and in the activity of cytochrome P450 omega/omega-1 arachidonate hydroxylases in kidneys of SHR. It is postulated that heme arginate treatment resulted in induction of heme oxygenase which consequently led to a diminution of cytochrome P450, especially the arachidonate omega/omega-1 hydroxylases leading to a marked decrease in 19-hydroxyeicosatetraenoic acid (HETE) and 20-HETE. The effect of heme arginate on blood pressure may be mediated via these biochemical events inasmuch as both 19-HETE and 20-HETE produced by the kidney may promote hypertension by causing vasoconstriction and sodium retention.

Animals↗
PubMed1989

Metabolism of 20-hydroxyeicosatetraenoic acid by cyclooxygenase. Formation and identification of novel endothelium-dependent vasoconstrictor metabolites.

We recently demonstrated that 20-hydroxyeicosatetraenoic acid (20-HETE) constricts rat aortic rings. The contractile response was partially dependent on the presence of endothelium and was abolished by pretreatment of the rings with either indomethacin or the endoperoxide/thromboxane receptor antagonist, SQ29548. Addition of GSH or SnCl2 to the organ bath diminished the contractile response of 20-HETE, whereas preincubation of the rings with a thromboxane synthase inhibitor did not affect the 20-HETE induced contractions. Short time incubation (2 min) of 20-HETE with ram seminal vesicle microsomes in the presence of p-hydroxymercurybenzoate yielded metabolites which migrated similarly on thin layer chromatography to the known arachidonate endoperoxides prostaglandin (PG) G2 and PGH2 and possess vasoconstrictory properties. The vasoconstriction was dose-dependent with a half-life of approximately 6.3 +/- 0.6 min. Addition of SQ29548 to the aortic ring bath 1 min after metabolite elicited vasoconstriction produced immediate relaxation. Furthermore, pretreatment of the rings with SQ29548 totally abolished the contraction. SnCl2 reduction of the metabolites produced in incubation of rat seminal vesicles with 20-HETE and p-hydroxymercurybenzoate resulted in a single radioactive peak which was further identified by gas chromatography/mass spectrometry as 20-hydroxy-PGF2 alpha. The inhibitory effect of SQ29548, the appearance of labile metabolites with a half-life of approximately 6 min and the production of 20-hydroxy-PGF2 alpha by SnCl2 reduction clearly indicate that the vasoconstrictor metabolites of 20-HETE are the labile endoperoxides of 20-HETE, 20-hydroxy-PGG2, and 20-hydroxy-PGH2.

Animals↗
PubMed1989

Treatment with tin prevents the development of hypertension in spontaneously hypertensive rats.

Cytochrome P-450-dependent metabolites of arachidonic acid (AA) increased in the kidneys of young, spontaneously hypertensive rats (SHRs) during the period of rapid elevation of blood pressure (BP) but not in adult SHRs or in Wistar Kyoto rats (WKYs) with normal BP. Treatment of SHRs and WKYs with stannous chloride (SnCl2), which selectively depletes renal cytochrome P-450, restored BP to normal, coincident with a natriuresis, in young but not in adult SHRs and did not affect either BP or sodium excretion in WKYs. Depletion of renal cytochrome P-450 was associated with decreased generation of these AA metabolites only in young SHRs. The antihypertensive effect of SnCl2 in young SHRs was greatly reduced by prevention of its cytochrome P-450-depleting action.

Animals↗
PubMed1989

Role of heme oxygenase in heme-mediated inhibition of rat brain Na+-K+-ATPase: protection by tin-protoporphyrin.

Hemoglobin has been shown to inhibit brain Na+-K+-ATPase through an iron-dependent mechanism. Both hemoglobin and iron cause spontaneous peroxidation of brain lipids. Release of iron from the heme molecule in animal tissues is dependent on the activity of heme oxygenase. We hypothesized that inhibition of heme catabolism by heme oxygenase prevents the iron-mediated inhibition of Na+-K+-ATPase and might subsequently reduce the tissue damage. Therefore, we studied the effect of heme and tin-protoporphyrin, an inhibitor of heme oxygenase, on the activity of partially purified Na+-K+-ATPase from rat brain in the presence and absence of purified hepatic heme oxygenase. Heme alone at a concentration of 30 microM did not inhibit Na+-K+-ATPase. However, in the presence of heme oxygenase, heme inhibited Na+-K+-ATPase by 75%. Pretreatment of rats with SnCl2, a known inducer of heme oxygenase, reduced the basal activity of the brain Na+-K+-ATPase by 50%. Inhibition of heme oxygenase by tin-protoporphyrin (30 microM) prevented the inhibition of Na+-K+-ATPase which occurred in the presence of heme and heme oxygenase. It is concluded that suppression of heme oxygenase by tin-protoporphyrin might be a therapeutic approach to management of hemoglobin-associated brain injury following CNS hemorrhage.

Animals↗
PubMed1989

Manipulation of cytochrome P-450 dependent renal thromboxane synthase activity in spontaneously hypertensive rats.

Thromboxane synthase is a cytochrome P-450-like enzyme requiring an iron-centered oxygen attack of the prostaglandin endoperoxide substrate (PGH2) for subsequent thromboxane A2 (TxA2) formation. The activity and levels of P-450 enzymes can be manipulated by decreasing heme availability. Stannous chloride (SnCl2) selectively induces renal heme oxygenase activity, depleting heme and decreasing hemoprotein synthesis. We therefore manipulated the renal cytochrome P-450 system to influence thromboxane synthase activity, as measured by the conversion of 14C-PGH2 to thromboxane B2 (TxB2) in renal cortical microsomes from spontaneously hypertensive rats (SHR). Seven-week-old SHR were treated subcutaneously with SnCl2 (1, 10 and 15 mg/100 g body weight) for 4 consecutive days, and cortical microsomal heme oxygenase activity, heme content, P-450 content, thromboxane synthase activity and systolic blood pressure were measured. Heme oxygenase activity was significantly increased from 1058 +/- 62 nmol/mg protein in controls to 3125 +/- 918, 5057 +/- 690--and 4236 +/- 581 nmol/mg protein in SHR treated with 1, 10 and 15 mg/100 g body weight SnCl2, respectively. The increase in heme oxygenase activity was associated with corresponding decreases in heme content (0.29 mumol/mg protein, for control to 0.12 mumol/mg protein for SHR treated with SnCl2, 10 mg/100 g body weight) and cytochrome P-450 content (0.18 +/- 0.1 nmol/mg protein for control to 0.06 +/- 0.01 nmol/mg protein for SHR treated with SnCl2 10 mg/100 g body weight). The reduction in heme and P-450 content was associated with a reduction in thromboxane synthase activity, i.e., decreases of 38, 35 and 47% from control levels at doses of 1, 10 and 15 mg/100 g body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Vasoactivity of 20-hydroxyeicosatetraenoic acid is dependent on metabolism by cyclooxygenase.

We recently demonstrated that cortical microsomes from spontaneously hypertensive rats metabolize arachidonic acid via cytochrome P450 to omega- and omega-1 hydroxylated compounds, 19- and 20-hydroxyeicosatetraenoic acids (HETE). The vascular activities of 20-HETE and the two isomers of 19-HETE were examined in rat aortic rings. The HETEs produced concentration-dependent contractions of the aortic rings. The contraction elicited by 20-HETE was abolished partially by removal of endothelium and was inhibited completely by treatment with indomethacin and reversed to a relaxation response by treatment with the endoperoxide and thromboxane receptor antagonist SQ 29548. These data suggest that the vascular effects of 20-HETE depend on subsequent metabolism by cyclooxygenase.

Animals↗
PubMed1988

19(S)-hydroxyeicosatetraenoic acid is a potent stimulator of renal Na+-K+-ATPase.

Omega- and omega-1 hydroxylations are the major pathways by which arachidonic acid is metabolized in cortical and outer medullary microsomes of rat and rabbit kidneys. It is a cytochrome P450-dependent oxidation leading to the formation of 20-hydroxy- and 19-hydroxyeicosatetraenoic acids. In this study, we compared the effects of the synthetically prepared omega- and omega-1 metabolites of arachidonic acid on the activity of the renal Na+-K+-ATPase partially purified from rat renal cortical microsomes. 19(S)-hydroxyeicosatetraenoic acid caused a dose related stimulation of Na+-K+-ATPase activity with an EC50 of 3 x 10(-7) M. In contrast, neither 19(R)-hydroxyeicosatetraenoic acid, 20-hydroxyeicosatetraenoic acid nor arachidonic acid at 10(-6) M had any effect on Na+-K+-ATPase activity. In the same preparation, ouabain at 10(-3) M and 12(R)-hydroxyeicosatetraenoic acid at 10(-6) M inhibited the enzyme activity by 75% and 60%, respectively. We conclude that 19(S)-hydroxyeicosatetraenoic acid is a specific stimulator of renal Na+-K+-ATPase. Therefore, the formation of 19(S)-hydroxyeicosatetraenoic acid by renal cortical cytochrome P450 omega-1-hydroxylase may contribute to the regulation of renal function by regulating Na+-K+-ATPase which is essential for transtubular transport processes.

Animals↗
PubMedDate not supplied

Cytochrome P-450 metabolites of arachidonic acid: implications for blood pressure regulation.

In the presence of NADPH cytochrome P-450-dependent monooxygenases oxidize arachidonic acid giving rise to four epoxyeicosatrienoic acids (EETs) which are hydrolyzed enzymatically to dihydroxyeicosatrienoic acids (DHETs). EETs generate vasodilators. Allylic oxidation forms hydroxyeicosatetraenoic acids, of which 12(R)HETE is an inhibitor of Na(+)-K(+)-ATPase and renin release. Finally, omega and omega-1 hydroxylation of arachidonic acid generates 20- and 19-HETEs which are involved in the development of hypertension in SHR rats.

Animals↗
PubMedDate not supplied

[The effects of digitalis compounds on K(+)-induced relaxation in aortic rings].

It has been shown that, changes in the structure of the cardiac glycoside, are related to changes in their biological effects. In the present study we compared the effects of two structurally different digitalis compound (ouabain and ouabagenin), on K+ induced vascular relaxation as an index of the Na+K+ ATPase activity. Ouabain was the most potent compound tested, and had vasoconstrictor effect on the rat aortic rings, as, well as inhibitory effect on the K(+)-induced relaxation. Ouabagenin did not affect either the vascular tone or K(+)-induced relaxation. It is well known that changes in the part of the structure of the cardiac glycoside that contain the sugar, are important to maintain some of their biological effects. In this paper we demonstrate that elimination of the 1-rhamnose in ouabagenin reduces its vascular effects associated to the inhibition of the Na+ K+ ATPase pump.

Animals↗