Biomedical subjects

M A Enero

Publications and source records attributed to M A Enero.

At least 37 records · Page 2Linked to original sources

PubMed1990

Cardiovascular responses to adrenergic agonists in sinoaortic denervated rats.

1. The cardiovascular effects of systemic alpha and beta adrenergic stimulation were studied in conscious sham-operated and sinoaortic denervated (SAD) rats, 7 days after the corresponding operation. 2. SAD does not modify the pressor response to phenylephrine (0.125-8 micrograms.kg-1, i.v.). The blood pressure increase was compensated for bradycardia in the sham-operated rats but not in the SAD. Only 8 micrograms.kg-1 of phenylephrine induced a slight fall of heart rate in the denervated animals. 3. The beta adrenergic agonist isoproterenol (7.8 ng.kg-1-2 micrograms.kg-1, i.v.) showed a greater hypotensive and a lesser tachycardic action in SAD than in sham-operated rats. However, these differences disappeared after autonomic ganglionic blockade (hexamethonium, 10 mg.kg-1, i.v.). 4. Our results suggest that after 7 days of SAD the pressor response to alpha adrenergic agonists may be unaltered and that the differences in the cardiovascular beta adrenergic response of SAD rats may be due to loss of the baroreflex mechanisms of cardiovascular compensation.

Adrenergic alpha-Agonists↗

PubMed1990

Effects of clenbuterol treatment on the responses to vasodilators in urethane-anaesthetized rats.

Seven or 14 days of treatment with the beta 2-adrenoceptor agonist clenbuterol, 0.3 mg kg-1, s.c., twice daily, increased the basal mean blood pressure in normotensive urethane-anaesthetized rats. The elevated pressure values were maintained until 48 h after the end of the 14 day treatment. Clenbuterol treatment decreased the vasodilatory responses to the beta-adrenoceptor agonist isoprenaline and adenosine, agents which act through an increase in intracellular cyclic AMP. Decreased responses were maintained until 48 h after a 14 day treatment with clenbuterol. On the other hand, its administration to rats for 14 days did not modify the vasodilator responses to acetylcholine or sodium nitroprusside, two agents that exert their effects by enhancing cyclic GMP. The increase in mean blood pressure in urethane-anaesthetized rats after clenbuterol treatment may be a consequence of a reduced vasodilator beta 2-adrenoceptor-mediated response to circulating catecholamines.

Acetylcholine↗

PubMed1990

Desensitization of the beta-2 adrenoceptor-mediated vasodilation in rat aorta after prolonged treatment with the beta-2 adrenoceptor agonist clenbuterol.

Administration to rats of the selective beta-2 adrenoceptor agonist (+/-)-clenbuterol (CLEN) (0.3 mg.kg-1 s.c., twice daily for 14 days) decreased the relaxant responses to the beta adrenoceptor agonist (-)-isoproterenol (IS) and to CLEN in KCl-contracted aortic rings. The treatment did not modify the vasodilation induced by forskolin (a direct activator of the catalytic subunit of the adenylate cyclase), 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor), adenosine or acetylcholine. IS increased (cAMP) cyclic AMP levels dose-dependently in rat aorta, and this effect was reduced markedly in arteries from CLEN-treated rats. By contrast, the treatment did not modify the forskolin-induced cAMP production. The contractile response to (-)-norepinephrine (NE) was inhibited in the presence of IS or CLEN in control aortic rings. However, this modulatory effect was not seen in arteries from CLEN-treated rats. Preincubation of the arteries with either cholera toxin (an activator of the stimulatory guanine nucleotide binding protein, Gs) or forskolin reduced NE-induced vasoconstriction to the same extent in aortic rings from both control and CLEN-treated rats. The chronotropic response to NE in rat atria (beta-1-mediated) was not affected by the treatment. These results suggest that prolonged administration of CLEN to rats induced desensitization of beta-2 adrenoceptor-mediated vascular relaxation by alterations at the level of the beta-2 adrenergic receptor, but not in the mechanisms related to Gs, adenylate cyclase or in those distal to cAMP production.

Animals↗

PubMed1989

Central muscarinic involvement in cardiovascular control in sinoaortic-denervated rats.

A study was made of the cardiovascular effects of centrally administered cholinergic drugs in conscious sham-operated or sinoaortic-denervated (SAD) rats. Neostigmine (0.01-1 micrograms) and bethanechol (0.125-2 micrograms), injected intracerebroventricularly (i.c.v.), induced a dose-dependent increase in mean blood pressure. This effect was significantly greater in SAD rats than in sham-operated rats. The heart rate was reduced by both neostigmine and bethanechol in sham-operated rats but remained unaltered in SAD animals. Similar doses of neostigmine and bethanechol injected i.v. did not have an effect in sham-operated rats. Central muscarinic blockade with methylatropine (1 or 5 micrograms i.c.v.) prevented the cardiovascular effects induced by neostigmine (1 microgram i.c.v.) in both groups of rats. The administration of methylatropine (0.3 mg/kg i.v.) to sham-operated rats only prevented the bradycardia induced by neostigmine (1 microgram i.c.v.), the pressor response was not affected. These results lend support to the view that cholinergic pathways are involved in the pressor and bradycardic responses of sham-operated rats and that they are mediated through central muscarinic receptors. The bradycardia induced by lower doses of the anticholinesterase, neostigmine, cannot be reflex-mediated. The fact that the pressor response to neostigmine was higher in SAD rats than in sham-operated animals could be either due to a different activity of the cholinergic pathways or to an abolition of baroreflex afferent activity. These results also suggest that there is a connection between central cholinergic pathways and baroreflex efferent activity.

Animals↗

PubMed1989

Interaction between clonidine and physostigmine in normal rats and in rats after sinoaortic denervation.

Clonidine (3-30 micrograms.kg-1, i.v.) induced a fall in mean arterial pressure in rats after sinoaortic denervation but not in sham-operated animals. Moreover, sinoaortic denervation reduced the bradycardic action of this antihypertensive drug. Pressor and tachycardic response to physostigmine (60 micrograms.kg-1, i.v.) were greater in denervated than in sham-operated rats. The increase of mean arterial pressure was 26.2 +/- 2.2 mm Hg in sham-operated rats (n = 12) and 53.8 +/- 2.0 mm Hg in denervated rats (n = 12, P less than 0.005). Pretreatment with 3 micrograms.kg-1 (i.v.) of clonidine did not alter the pressor response to physostigmine (60 micrograms.kg-1) in either of the two groups; 10 and 30 micrograms.kg-1 of clonidine reduced the physostigmine-induced increase of mean arterial pressure in sham-operated rats but enhanced the pressor response in denervated animals. Furthermore, an ineffective dose of physostigmine (30 micrograms.kg-1, i.v.) induced a pressor response after pretreatment with clonidine (10 micrograms.kg-1) in denervated rats. Clonidine (10 micrograms.kg-1) did not affect the pressor effect of 1,1 dimethyl-4-phenylpiperazinium iodide (DMPP: 50 micrograms.kg-1, i.v.) or phenylephrine (4 micrograms.kg-1, i.v.) in either group. The anticholinergic effect of clonidine in sham-operated rats may be explained by an inhibitory action on the release of acetylcholine in several brain structures but the facilitatory effect of clonidine observed in denervated animals is not clear. The results did not suggest a peripheral involvement in this facilitatory effect.

Animals↗

PubMed1989

Modulation of noradrenaline release by presynaptic alpha-2 and beta adrenoceptors in rat atria. Effect of pretreatment with clenbuterol.

The effect of pretreatment with the beta-2-selective adrenoceptor agonist, (+/-)-clenbuterol (0.3 mg/kg, twice daily, 14 days) on prejunctional alpha-2- and beta-adrenoceptors was studied in rat atria. When atria from non-pretreated rats had been preincubated with (3H)-noradrenaline, (-)-isoprenaline (0.02 to 4.0 microM) did not affect tritium overflow evoked by stimulation of the cardioaccelerant nerves, but a higher concentration (40 microM) decreased it. Blockade of prejunctional inhibitory alpha-2-adrenoceptors by yohimbine (0.03, 0.3 and 0.8 microM) enhanced the overflow of tritium. In the presence of yohimbine, isoprenaline (1.2 microM) significantly increased stimulation-induced transmitter overflow, suggesting that in rat atria the facilitatory effect of isoprenaline mediated via prejunctional beta-adrenoceptors, is masked by the dominant influence of inhibitory alpha-2-adrenoceptors. (-)-Propranolol (0.1 microM) prevented the isoprenaline-induced increase in atrial rate and the isoprenaline-induced enhancement of transmitter release in the presence of yohimbine (0.3 microM), but did not modify by itself the stimulation-induced efflux of tritium, suggesting that neuronally released noradrenaline failed to activate facilitatory prejunctional beta-adrenoceptors. When atria from clenbuterol-pretreated rats had been preincubated with 3H-noradrenaline, the facilitatory effect of yohimbine 0.03 and 0.3 microM was markedly enhanced and, in this case, isoprenaline (1.2 and 12.0 microM) failed to cause its facilitatory effect in the presence of the alpha-2-adrenoceptor antagonist. Propranolol did not modify the facilitatory effect of yohimbine. No changes in the isoprenaline-induced increase in atrial rate were observed in clenbuterol-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Stimulation of Na+,K+-ATPase activity in certain membranes of the rat central nervous system (CNS) by acute administration of desipramine (DMI).

1. The activities of ATPase in rat CNS were studied 3 hr after administration of the noradrenaline uptake inhibitor, desipramine (DMI: 10 mg.kg-1, i.p.). Na+K+-ATPase activity significantly increased after DMI in the whole particulate from hypothalamus and mesencephalus but no changes in frontal cortex or in pons-medulla oblongata areas were found. This increase was prevented when the animals were pretreated with the noradrenergic neurotoxic N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). 2. Purified membrane fractions from hypothalamus were obtained by differential and sucrose gradient centrifugation (0.8-1.2 M sucrose). It was observed that after DMI, Na+,K+-ATPase activity increased only in the membranous fraction lying at 0.9 M sucrose. 3. Mg2+- or Ca2+-ATPase activities were not modified by DMI treatment. 4. Citalopram, a specific serotonergic uptake inhibitor, did not affect ATPase activities. 5. The results obtained could indicate that DMI acute administration selectively stimulates Na+,K+-ATPase activity of certain membranes of the CNS after an increase in the concentration of the noradrenergic neurotransmitter in the synaptic gap.

Animals↗

PubMed1989

Further evidence of interaction between vasodilator beta 2- and vasoconstrictor alpha 2-adrenoceptor-mediated responses in maintaining vascular tone in anesthetized rats.

The importance of the interaction of alpha- and beta-adrenoceptors in maintaining vascular tone in rats was studied. This interaction after clenbuterol (CLEN) treatment indicates an important contribution of the circulating epinephrine (EPI) levels. In urethane-anesthetized rats, the beta 2-adrenoceptor antagonist ICI 118.551 was more effective in antagonizing isoproterenol-induced hypotension (mainly beta 2-mediated) than tachycardia (mainly beta 1-mediated). Intravenous (i.v.) administration of the alpha 2-adrenoceptor agonist clonidine (CLO) induced an initial pressor response followed by a more prolonged hypotension and bradycardia. The initial hypertensive effect was potentiated by previous acute administration of ICI 118.551 as well as by the nonselective beta-adrenoceptor antagonist propranolol, but not by metoprolol, a more selective beta 1-blocker. Fourteen days of administration of the beta 2-adrenoceptor agonist CLEN [0.3 mg/kg, subcutaneously (s.c.) twice daily], a treatment that induces desensitization of beta 2-mediated vasodilation, increased the pressor response induced by CLO, an effect that was not observed in pentobarbital-anesthetized rats. In any case, neither beta-blockers nor CLEN treatment affects the hypotension and bradycardia induced by CLO. Mean blood pressure (BP) of CLEN-treated rats was increased under urethane anesthesia but not under pentobarbital anesthesia. Catecholamine levels (principally EPI) were higher in urethane-anesthetized rats. These results provide further evidence of a functional interaction between alpha 2- and beta 2-adrenoceptor-mediated responses in rat vasculature and suggest that vasodilator beta 2-adrenoceptors might contribute to the determination of peripheral vascular tone when circulating EPI is substantially elevated.

Anesthesia↗

PubMed1989

Pressor response induced by clenbuterol treatment in immobilized normotensive rats.

Short-term treatment with clenbuterol [0.6 mg/kg-1 subcutaneously (s.c.) daily] produces a pressor effect in stressed rats after a period of immobilization (40 min). The stress applied markedly increases the plasma concentrations of norepinephrine (NE) and epinephrine. After bilateral adrenal demedullation, the increased levels of catecholamines and the hypertensive response obtained after clenbuterol treatment in the stressed animals were reduced to the values of the control rats. Clenbuterol treatment produced desensitization of the beta 2-adrenoceptor-mediated effect and thus reduced the vasodilator response induced by isoproterenol and increased the vasoconstriction produced by epinephrine but not that caused by NE. This desensitization may be responsible for the hypertensive response after clenbuterol treatment in stressed animals which is attenuated after adrenal demedullation. In conclusion, our results provide evidence that clenbuterol treatment induces pressor effect in normotensive animals under stress.

Adrenal Medulla↗

PubMed1988

GABAergic mechanism involved in sinoaortic denervation in rats.

GABAergic neurotransmission in sinoaortic denervated (SAD) rats with that in sham-operated animals 15 days after operation. In sham-operated rats, glutamic acid decarboxylase (GAD) and 4-amino-butyrate-2-oxoglutarate aminotransferase (GABA-T) activities were higher in dorsal than in ventral regions of pons and medulla oblongata and a higher GAD activity was observed in anterior than in posterior hypothalamus. Fifteen days after SAD, GAD and GABA-T activities were significantly reduced in dorsal pons and in anterior hypothalamus whereas GABA-T activity was increased in ventral medulla oblongata. The results indicate the involvement of GABAergic neurotransmission in the deafferentation of the nucleus tractus solitarii by sinoaortic denervation. GABA hypothalamic inputs could be involved in the baroreflexes.

4-Aminobutyrate Transaminase↗

PubMed1988

Effects of prostaglandin F2 alpha on vasoconstrictor responses in the mesenteric vascular bed.

Prostaglandin F2 alpha (PGF2 alpha) in a concentration that did not induce vascular contraction (10(-8) M) potentiated the dose-response curves to norepinephrine and 5-hydroxytryptamine and the contractile response induced by potassium (60 or 100 mM) in isolated mesenteric vascular bed of the rat. After prostaglandin inhibitor treatment with indomethacin (10(-6) M), the dose-response curve to norepinephrine was reduced, and the dose (10(-10) M) of PGF2 alpha, which was ineffective in control tissues, facilitated the norepinephrine contractile response. In contrast, indomethacin did not change either the contractile response induced by potassium or the PGF2 alpha potentiation of this response. Calcium antagonists diltiazem or flunarizine reduced the potassium-induced contractile response. After diltiazem treatment, 10(-10) M of PGF2 alpha was also effective in facilitating this response. The PGF2 alpha postjunctional effect was conserved after phosphoinositide hydrolysis inhibition. These results suggest that PGF2 alpha potentiation of the contractile response may be independent of PGF2 alpha contraction. Low doses of endogenous prostaglandins could be able to facilitate the norepinephrine contractile response in this tissue. This process may be independent of calcium influx and phosphoinositide hydrolysis.

Animals↗

PubMed1988

Studies on the GABAergic system in cardiovascular control in normotensive and in sinoaortic denervated rats.

The cardiovascular effects of i.v. gamma-amino-beta-hydroxybutyric acid (GABOB) were investigated in rats anaesthetized with urethane. GABOB produced a dose-dependent hypotensive response. Treatment with GABA-A receptor antagonists prevented the GABOB response while the GABA stimulation by diazepam enhanced this response. The beta 1-adrenoceptor antagonist reduced the GABOB-induced hypotension but beta 2-adrenoceptor antagonists did not affect it. Picrotoxin, bicuculline or diazepam produced an increase in basal blood pressure. Fifteen days after sinoaortic denervation in rats the glutamic acid decarboxylase and the aminobutyric acid transaminase (GABA-T) activities were significantly reduced in dorsal pons and in anterior hypothalamus whereas GABA-T activity was increased in ventral medulla oblongata. Our results demonstrate that GABOB stimulates GABA-A receptors in anaesthetized rats and thus exerts a neuromodulatory effect on cardiovascular function. GABAergic neurotransmission participates in the sinoaortic deafferentation in rats.

4-Aminobutyrate Transaminase↗

PubMed1988

Influence of a receptor reserve on the inhibition by calcium channel blockers of alpha adrenoceptor-mediated responses in rat isolated vascular tissues.

The effects of the Ca entry blockers nifedipine and verapamil on the contractions induced by phenylephrine (PHE) in rat isolated aorta and mesenteric vascular bed (MVB) were evaluated. The main goal was to elucidate whether differences among blood vessels in their receptor reserves are involved in the different degrees to which Ca antagonists inhibit alpha adrenergic vasoconstriction. In the two tissues the responses to the full agonist PHE were antagonized by prazosin with an at least 1000-fold greater potency than by yohimbine. The -log KB values for both antagonists in the aorta (11.07 and 7.40, respectively) were significantly higher than those in the MVB (9.77 and 6.43, respectively), thus suggesting receptor heterogeneity between the two tissues. Both nifedipine and verapamil were more effective in reducing the responses in the MVB (maximal inhibition, 54.3 +/- 1.9 and 55.0 +/- 3.5%) than in the aorta (25.2 +/- 5.8 and 30.4 +/- 0.7%). Studies with phenoxybenzamine (PB) indicated that in the latter case the responses were associated with an effective receptor reserve of about 40%, whereas in the MVB no spare receptors for the full agonist were available. Pretreatment of the MVB with PB showed no effect on the inhibitory action of verapamil. Conversely, removal of the spare receptors in the aorta (10(-10) M PB) rendered the responses more susceptible to inhibition by verapamil. Pretreatment of the aortic strips with 10(-9) M PB, however, failed to enhance further the effectiveness of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Sinoaortic denervation: serotonergic and cholinergic participation.

1. This review describes the role of serotonergic and cholinergic pathways in blood pressure regulation after sinoaortic denervation of rats. 2. The changes observed in serotonergic activity were related to the development and/or the maintenance of neurogenic hypertension. 3. The data indicate that baroreceptor deafferentation could affect the peripheral parasympathetic tone which regulates heart rate. 4. Moreover, there is evidence that brain cholinergic neurons may be involved in the process of neurogenic hypertension produced by sinoaortic denervation.

Acetylcholine↗

PubMed1987

Different pharmacological interaction of clonidine and guanabenz with antidepressive drugs.

A study was made of the effect of several antidepressive drugs with different mechanisms of action on cardiovascular response induced by clonidine (CLO) or guanabenz (GUA) in anaesthetized normotensive rats. The acute pretreatment (1 mg.kg-1) with desipramine (DMI), maprotiline (MAP) and mianserin (MIA) reduced the hypotensive and bradycardiac responses induced by CLO (10 micrograms.kg-1), while only MIA prevented these central actions when elicited by GUA (30 micrograms.kg-1). Only chronic treatment with DMI reduced the hypotensive effect of CLO, but none of long-term antidepressant administrations decreased the fall in blood pressure induced by GUA. The long-term administration of DMI, MAP and MIA abolished the bradycardia from both agonists, CLO and GUA. The different pharmacological interaction of CLO and GUA with (acute or chronic) antidepressive treatments could be explained by a structural difference between the two agonists, and also by differences in localization and/or subtype of the alpha-adrenoceptors involved in their central cardiovascular effects.

Animals↗

PubMed1986

Interaction between beta 2- and alpha 2-adrenoceptor responses in the vascular system: effect of clenbuterol.

Subchronic treatment with the beta 2-adrenoceptor agonist, clenbuterol (0.3 mg X kg-1, twice daily for 14 days), significantly increased the median blood pressure in anaesthetized normotensive rats. The treatment produced a marked reduction in the vasodilator effect of isoproterenol. Acute clenbuterol administration (0.01 mg X kg-1 i.v.) reduced the contractile response induced by the alpha 2-adrenoceptor agonists, guanabenz or B-HT 920, and the alpha 1- and alpha 2-adrenoceptor agonist, clonidine, whereas it did not affect the vasoconstriction by the alpha 1-adrenoceptor agonist, methoxamine, in the pithed rat. Subchronic treatment with clenbuterol attenuated the effect of the beta 2-adrenoceptor agonist on the vascular alpha 2-adrenoceptor responses and enhanced the alpha 1-adrenoceptor response to phenylephrine in pithed rats. The effect of the beta 2-adrenoceptor agonist was reduced by 1- but not d-propranolol. These results suggest that subchronic treatment with clenbuterol produces a subsensitivity of the beta 2-adrenoceptors and reduced the interaction between beta 2- and alpha 2-adrenoceptors at the vascular wall.

Animals↗

PubMed1986

Cardiovascular effects of alpha-adrenergic drugs: differences between clonidine and guanabenz.

Guanabenz induced a pressor effect in pithed rats through postsynaptic alpha 2-adrenoceptors whereas clonidine activated both vascular alpha 1 and alpha 2-adrenoceptors. Previous treatment with prazosin, an alpha 1-antagonist, or depletion of the noradrenergic stores by reserpine produced supersensitivity to the pressor response to clonidine only, probably through postsynaptic alpha 1-adrenoceptors. The hypotension and bradycardia developed in normotensive rats after intravenous guanabenz administration were abolished by prazosin, whereas the central effects of clonidine were antagonized by both prazosin and yohimbine. Selective destruction of central noradrenergic neurons by [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] (DSP 4) or reserpine plus blockade of catecholamine synthesis by alpha-methyl-p-tyrosine abolished the hypotension and bradycardia produced by guanabenz but merely reduced the bradycardia from clonidine. The present results suggest that, in rats, guanabenz is a selective stimulant of central alpha-autoadrenoceptors antagonized by prazosin whereas at a vascular level guanabenz preferentially activates alpha-adrenoceptors antagonized by yohimbine. The differences observed between the mechanisms by which guanabenz and clonidine produce their central cardiovascular responses might be attributed to their acting on different nuclei.

Animals↗

PubMed1986

Increase of alpha 2-presynaptic adrenoceptor response after neuronal uptake inhibition in vivo.

alpha 2-adrenoceptor antagonists, yohimbine or idazoxan (1 mg kg-1 i.p.), administered alone, did not change noradrenaline content in the central and peripheral tissues of the rat (hypothalamus, brain stem, frontal cortex and heart). The inhibition of neuronal uptake by desipramine (DMI) administered alone or prior to alpha 2-adrenoceptor antagonists did not affect the neurotransmitter content either. alpha-methyl-p-tyrosine (alpha-MT) 6 hr before sacrifice, induced a marked disappearance of the noradrenaline content, greater in central nervous tissues than in heart. When the catecholamine synthesis was inhibited by alpha-MT, neither alpha 2-adrenoceptor antagonists nor DMI at the dose used, significantly changed the disappearance rate of noradrenaline in any of the tissues studied. Under these experimental conditions, however, the combination of DMI plus alpha 2-adrenoceptor antagonists significantly decreased the neurotransmitter content in all tissues when the values were compared with the control or DMI-treated groups. The present results might suggest evidence in favour of a functional coupling between presynaptic alpha 2-autoreceptors and noradrenaline uptake mechanism.

Animals↗