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Biomedical subjects

F J Miranda

Publications and source records attributed to F J Miranda.

At least 37 records · Page 2Linked to original sources
PubMed1991

Ca2+ entry blockers inhibit prostaglandin F2 alpha-induced cerebrovascular contractile responses in goats.

We examined the effects of extracellular Ca2+ withdrawal and of Ca2+ entry blockers on goat cerebrovascular responses to prostaglandin F2 alpha (PGF2 alpha). We measured isometric tension in isolated middle cerebral arteries, and cerebral blood flow (CBF) in unanesthetized animals. PGF2 alpha produced concentration-dependent contractions of isolated arteries. The contractions were partially inhibited by incubation in Ca(2+)-free medium (by 63.1 +/- 1.8% without ethyleneglycol-bis-(beta-amino-ethylether)-N,N,N',N'-tetra-a cetate (EGTA), and by 82.4 +/- 3.7% with EGTA). The Ca2+ entry blockers inhibited PGF2 alpha-elicited contraction and relaxed PGF2 alpha-precontracted arteries (nicardipine, 91.4 +/- 9.8%; nimodipine, 73.1 +/- 2.0%; and verapamil, 50.5 +/- 4.5% relaxation of the active tone). Injection of PGF2 alpha into the cerebral circulation produced dose-dependent reductions in CBF (34.4 +/- 2.1% after 30 micrograms) which were inhibited during infusion of Ca2+ entry blockers (nicardipine 10 micrograms/min, 14.7 +/- 1.5%; nimodipine 10 micrograms/min, 13.6 +/- 1.3%; and verapamil 100 micrograms/min, 13.7 +/- 2.3% of flow reduction). We conclude that PGF2 alpha-elicited contraction of goat cerebral arteries is mainly mediated by extracellular Ca2+ influx through Ca2+ channels sensitive to Ca2+ entry blockers. The anticonstrictor effects of Ca2+ entry blockers observed in vitro are consistent with their inhibitory effect on the PGF2 alpha-induced CBF reductions.

Animals↗
PubMed1991

Effects of endothelin-1 on the cerebrovascular bed of the goat.

The aim of the present study was to analyze the effects of endothelin-1 (ET-1) in the cerebrovascular bed of the goat, the importance of endothelial integrity and the contribution of extracellular Ca2+ to these responses. We measured isometric tension and 45Ca2+ uptake in isolated middle cerebral arteries, and cerebral blood flow (CBF) in unanesthetized animals. ET-1 elicited concentration-dependent contractions which were potentiated in arteries without endothelium. Ca2(+)-free medium and nicardipine inhibited, and Bay K 8644 potentiated the ET-1-induced contractions. ET-1 enhanced 45Ca2+ uptake in isolated arteries. Injections of ET-1 directly into the cerebral circulation decreased CBF and increased cerebrovascular resistance in a dose-dependent manner. Infusion of nicardipine inhibited the ET-1-induced reductions in CBF. These results suggest that ET-1 reduces CBF of goats because of contraction of cerebral arteries by a direct action on smooth muscle, which is modulated by the endothelium and depends partially on the activation of Ca2+ influx through dihydropyridine-sensitive channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

In vivo and in vitro effects of magnesium sulfate in the cerebrovascular bed of the goat.

The effects of magnesium sulfate in the cerebrovascular bed were studied both in vivo, by measuring cerebral blood flow in conscious nonpregnant goats, and in vitro, by recording isometric tension in isolated goat middle cerebral arteries. Injections of increasing doses (10 to 300 mg) of magnesium sulfate directly into the cerebral circulation elicited transient and dose-dependent increases in cerebral blood flow and decreases in cerebral vascular resistance. Similar results were obtained when increasing doses (0.3 to 3 gm/15 min) of magnesium sulfate were infused intravenously, although the vasodilatations reached a stable plateau that remained when the infusions finished. Cumulative addition of magnesium sulfate (10(-5) to 3 x 10(-2) mol/L) did not change the isometric tension of isolated arterial segments at resting tone, but relaxed in a concentration-dependent manner the arterial segments preconstricted with 10(-5) mol/L prostaglandin F2 alpha. These results demonstrate that magnesium sulfate acts as a dilator in the cerebral circulation by acting directly on the cerebral arteries. This could explain, at least in part, its beneficial effects on preeclampsia-eclampsia.

Animals↗
PubMed1991

Modulatory action of acetylcholine on cerebrovascular sympathetic neurotransmission.

1. Acetylcholine (10 micrograms/min) diminished the electrically-induced cerebral blood flow reductions. Atropine (1-2 mg) partially blocked this inhibitory effect. 2. Exogenously administered noradrenaline (1-10 micrograms) and tyramine (50-500 micrograms) reduced cerebral blood flow but this effect was unchanged by acetylcholine infusion. 3. Acetylcholine inhibited the nonadrenergic component of the electrically-induced contraction at a concentration greater than or equal to 10(-6) M and potentiated the adrenergic component at a concentration greater than or equal to 10(5) M. Atropine 10(-7) M) inhibited both of these effects. In addition, acetylcholine (10(-4) M) enhanced the electrically-evoked [3H]noradrenaline overflow. 4. These results show that: (a) acetylcholine modulates cerebrovascular sympathetic neurotransmission by acting on muscarinic receptors; and (b) the potentiating effect of acetylcholine is achieved by a mechanism involving increases in noradrenaline release.

Acetylcholine↗
PubMed1990

Effects of Ca2+ entry blockers on CaCl2-, KCl- and noradrenaline-induced contractions of goat cerebral arteries.

The effects of three Ca2+ entry blockers, nicardipine, nimodipine and verapamil, on CaCl2-, KCl- and noradrenaline-induced contractions were examined in isolated goat middle cerebral artery. The relationship between the effects of Ca2+ entry blockers and the extracellular Ca2+ dependence of the contractions was also examined. In 'nominally' Ca2(+)-free medium, addition of CaCl2 induced concentration-dependent contractions of previously depolarized arteries. Withdrawal of Ca2+ from the extracellular medium caused strong inhibition of the KCl- and noradrenaline-induced arterial contractions. Addition of EGTA to the Ca2(+)-free medium almost abolished the noradrenaline-response but did not increase the inhibition of the KCl-induced contractions. The Ca2+ entry blockers induced concentration-dependent relaxation of the precontracted arteries (100 mM KC1) with the following order of potency: nimodipine greater than nicardipine greater than verapamil. The CaCl2-, KCl- and noradrenaline-induced contractions were depressed in a concentration-related manner by nicardipine, nimodipine and verapamil. Dihydropyridines showed a greater inhibitory effect than verapamil. These results show that Ca2+ entry blockers are able to inhibit the contractile responses of goat cerebral arteries to KCl and noradrenaline, an effect which may be explained by the strong dependence of both responses on extracellular Ca2+.

Animals↗
PubMed1990

Heterogeneity of P2-purinoceptors in brain circulation.

The existence of P2-purinoceptors in the cerebrovascular bed was examined by testing the effects of ATP and its stable analog, alpha, beta-methylene-ATP, on CBF in the unanesthetized goat as well as on isometric tension in isolated goat middle cerebral artery. When injected directly into the cerebral circulation, ATP increased and alpha, beta-methylene-ATP decreased CBF. Indomethacin did not modify either of these effects. The vasoconstrictor action of alpha, beta-methylene-ATP was reduced by nicardipine. "In vitro," both ATP and alpha, beta-methylene-ATP contracted the cerebral arteries at resting tone, but the analog was more potent than ATP. Repeated application of alpha, beta-methylene-ATP as well as indomethacin significantly reduced the ATP-induced contractions. Nicardipine inhibited both the alpha, beta-methylene-ATP- and the ATP-induced contractile response. In preconstricted arteries, ATP produced relaxation and alpha, beta-methylene-ATP induced further contraction. The relaxant response to ATP was not modified by indomethacin. These results show the existence of two subtypes of P2-purinoceptors in brain circulation: P2x, more sensitive to alpha, beta-methylene-ATP than to ATP, which elicits cerebral vasoconstriction; and P2y, sensitive to ATP, which elicits cerebral vasodilation.

Adenosine Triphosphate↗
PubMed1989

Inhibitory effect of GABA on cerebrovascular sympathetic neurotransmission.

The possibility that gamma-aminobutyric acid (GABA) could modulate sympathetic neurotransmission in the cerebrovascular bed of the goat has been investigated by means of 3 experimental approaches: measurement of cerebral blood flow in the anesthetized animal, recording of isometric tension in isolated cerebral arteries, and measurement of tritium efflux from cerebral arteries preloaded with [3H]noradrenaline. Electrical stimulation of cervical sympathetic nerve produced reductions in cerebral blood flow which were significantly diminished during continuous infusion of GABA (20-40 micrograms/min) into the internal maxillary artery. Picrotoxin (3 mg) did not change the inhibitory effect of GABA. Exogenously administered noradrenaline (1-9 micrograms) and tyramine (50-500 micrograms) reduced cerebral blood flow as well, but this effect was unchanged by GABA infusion. Transmural electrical stimulation elicited frequency-dependent contractile responses in isolated cerebral arteries which were significantly blocked when GABA was present, at a dose (10(-4) M) which did not modify the contractile response to exogenous noradrenaline (10(-8)-10(-4) M). Moreover, GABA (10(-5)-10(-4) M) inhibited transmural electrical stimulation-evoked tritium efflux from arteries preloaded with [3H]noradrenaline. These results show that GABA inhibits adrenergic neurotransmission in cerebral arteries by a mechanism involving inhibition of transmitter release. Probably, specific presynaptic GABA-B receptors mediate this inhibitory effect.

Adrenergic Fibers↗
PubMed1988

P1-purinoceptors in the cerebrovascular bed of the goat in vivo.

The possible existence and function of specific P1-purinoceptors in the cerebrovascular bed of the unanesthetized goat have been investigated. Blood flow to one cerebral hemisphere (cerebral blood flow) was measured by means of an electromagnetic flow probe previously implanted around the ipsilateral internal maxillary artery. The injection of adenosine, AMP, ADP and ATP (3-30 micrograms) directly into the internal maxillary artery increased cerebral blood flow and decreased cerebrovascular resistance in a dose-dependent manner. Continuous infusion of 8-phenyltheophylline (8-PT), 100 micrograms/min, into the internal maxillary artery did not alter the resting cerebral blood flow or the cerebrovascular resistance, but significantly inhibited the cerebral vasodilation induced by adenosine, AMP, ADP and, to a lesser degree, ATP. The acetylcholine- and histamine-induced cerebral vasodilation was unaffected by 8-PT. These results indicate that adenosine, AMP, ADP and, at least in part, ATP increase cerebral blood flow by acting on specific P1-purinoceptors located in the cerebrovascular wall. These P1-purinoceptors do not appear to be tonically activated under physiological conditions.

Adenosine↗