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Biomedical subjects

R Mosqueda-Garcia

Publications and source records attributed to R Mosqueda-Garcia.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cardiovascular effects of endothelin injected into brain nuclei regulating vasopressin release.

We studied the cardiovascular effects produced by administration of endothelin-1 (ET-1) into brain nucleic known to affect vasopressin release. In urethane-anesthetized Sprague-Dawley rats, microinjection of ET-1 into the subfornical organ (SFO) resulted in a dose-dependent increase in arterial blood pressure and a decrease in heart rate. These effects were inhibited by previous administration of the ETA receptor antagonist BQ-123 or by intravenous administration of a vasopressin antagonist. In addition, microinjection of ET-1 into the SFO increased plasma levels of vasopressin. In contrast, in the paraventricular nucleus (PVN) of the hypothalamus microinjection of ET-1 evoked a dose-related bradycardia with inconsistent changes in blood pressure. Although the bradycardia was antagonized by intra-PVN administration of BQ-123, the vasopressin antagonist did not affect the changes in heart rate evoked by microinjection of this peptide into the PVN. Overall, these results indicate that the central cardiovascular effects of ET-1 result from activation of several mechanisms, including stimulation of brain centers regulating vasopressin release.

Animals↗
PubMed1994

Inhibition by ethanol of the cardiovascular effects of glutamate in the nucleus of the solitary tract.

This study investigates whether ethanol affects the cardiovascular changes evoked by the excitatory amino acid glutamate in the nucleus of the solitary tract (NTS). Male Sprague-Dawley rats were anesthetized with urethane and instrumented for microinjection of drugs into the NTS. In 28 animals, an initial dose-response curve for glutamate (37, 74, and 148 pmol/60 nL) was obtained. In eight animals (control group), the dose-response curve was unchanged when it was tested after microinjection of 60 nL of saline into the NTS. In contrast, the prior intra-NTS administration of ethanol (25 or 50 mM) consistently inhibited the hypotensive and bradycardic effects of glutamate. The specificity of this inhibitory response was corroborated by the inability of intra-NTS administrations of ethanol (50 mM) to affect the hypotensive and bradycardic responses to nicotine (922 pmol. 1.84 nmol, and 3.96 nmol). These results indicate that the cardiovascular effects of glutamate can be antagonized by ethanol in the NTS. This inhibitory effect, in turn, may provide a basis for the hypertensinogenic action of ethanol in humans.

Animals↗
PubMed1993

The diagnosis and treatment of baroreflex failure.

BACKGROUND: Baroreflexes originate in the great vessels of the neck and thorax and prevent arterial pressure from rising or falling excessively. METHODS: This study was undertaken to clarify the cause, clinical spectrum, and therapy of this disorder. We studied 11 patients with baroreflex failure presenting as severe, labile hypertension and hypotension, often with headache, diaphoresis, and emotional instability, and characterized by the failure of exogenous vasoactive substances to alter heart rate. Each underwent hemodynamic monitoring and biochemical, physiologic, and pharmacologic testing. RESULTS: The patients' maximal systolic blood pressures ranged from 164 to 280 mm Hg, and their minimal systolic pressures ranged from 58 to 96 mm Hg. Plasma norepinephrine and epinephrine concentrations were sometimes many times normal during blood-pressure surges. All the patients had excessive pressor and tachycardia responses to the mental-arithmetic and cold pressor tests and marked hypersensitivity to clonidine. The underlying causes of baroreflex failure included the familial paraganglioma syndrome, neck surgery or radiation therapy for pharyngeal carcinoma, bilateral lesions of the nucleus tractus solitarii, and surgical section of the glossopharyngeal nerves; in two patients the cause was unknown. Therapy with clonidine reduced the frequency of attacks by 81 percent and attenuated the elevated blood pressure and heart rate in the attacks that occurred. CONCLUSIONS: The syndrome of baroreflex failure should be considered in patients with otherwise unexplained labile hypertension. Clonidine attenuates the pressor and tachycardic surges in baroreflex failure.

Adult↗
PubMed1993

Central cardiovascular effects of joining peptide in genetically hypertensive rats.

Joining peptide (JP) is one of the major products of proopiomelanocortin (POMC). The biological function of this peptide has not been clarified despite its relative abundance in the pituitary and the hypothalamus. Recently we demonstrated that JP, which was isolated from bovine posterior pituitary, possesses Na pump inhibitor activity. The purpose of this study is to explore the physiological relevance of JP in cardiovascular regulation. For these investigations, we used the synthetic peptides bovine JP (bJP) and COOH-terminally amidated rat JP (rJP), since JP is known to have sequence variability among species. Intracisternal administration of both bJP and rJP in urethan-anesthetized rats evoked similar hypertensive and tachycardia effects. The effects of both peptides were markedly greater in the spontaneously hypertensive rats (SHR) compared with the normotensive Wistar Kyoto rats (WKY). Intravenous bolus injections of rJP at the same doses were without effect. Autoradiography, using 125I-labeled [0Tyr]-rJP as a ligand, revealed specific binding sites for rJP in the dorsal medulla in areas corresponding to the nucleus tractus solitarii (NTS) (extending from approximately 0.4 mm caudal to 1.8 mm rostral to the obex). Microinjections of rJP into the caudal part of the NTS of anesthetized SHR produced dose-related pressor and tachycardic responses. The pressor and tachycardic responses were also observed at the rostral part of the NTS, whereas the injections into the intermediate part of the NTS evoked depressor and bradycardic responses in SHR. These results suggest that at doses tested, the site of JP action resides in the central nervous system, and that JP is a potent neuropeptide in medullary sites known to be pivotal in central cardiovascular regulation. The effect of JP is especially prominent in the genetically hypertensive rat.

Analysis of Variance↗
PubMed1993

Endothelin as a neuropeptide. Cardiovascular effects in the brainstem of normotensive rats.

The relevance of endothelin in central cardiovascular function was studied in urethane-anesthetized Sprague-Dawley rats. Blood pressure (BP) was monitored intra-arterially, and cerebrospinal fluid (CSF) was collected through an intracisternal catheter for radioimmunoassay of endothelin-1 (ET-1). Endothelin levels in the CSF were significantly higher (39 +/- 3 pg/ml) than in plasma (10 +/- 3 pg/ml, n = 11). ET-1 in CSF or plasma was not affected by systemic infusion of saline, but its levels significantly decreased when a sustained increase in BP was elicited with phenylephrine (14 +/- 7 pg/ml in the CSF and 6 +/- 4 pg/ml in plasma, n = 5). In sinoaortic-denervated animals, phenylephrine failed to reduce CSF endothelin levels. In different experiments, intracisternal administration of ET-1 (10 pmol) evoked an initial decrease in BP and heart rate (HR), followed by pronounced hypertension, bradycardia, and, in 70% of the animals, death from cardiorespiratory failure. Intracisternal administration of endothelin-3 (ET-3, 80 pmol, n = 11) evoked only a modest hypotensive and bradycardic response without cardiorespiratory impairment. Microinjection of ET-1 (0.5, 1, 2, 4, and 6 pmol/60 nl) into the nucleus of the solitary tract or area postrema produced a decrease in BP and HR. On the other hand, injection of low concentrations of ET-3 into the nucleus of the solitary tract increased BP and HR (at 2 pmol, 17 +/- 3 mm Hg, 14 +/- 6 beats per minute, n = 7), whereas ET-3 in the area postrema produced a prominent dose-related decrease in BP and HR. In the rostroventrolateral medulla, the lowest doses of ET-1 first modestly increased BP and renal sympathetic nerve activity. These effects were followed by hypotension, bradycardia, increase in respiratory frequency, and further enhancement of sympathetic nerve traffic. In 29% of the animals, these effects were followed by cardiorespiratory arrest. The specificity of the cardiovascular response to endothelin was demonstrated by the inhibitory effects of the receptor antagonist BQ-123. These results demonstrate that endothelin has specific cardiovascular effects in the brainstem of the rat and support a role for endothelin in cardiovascular regulation.

Animals↗
PubMed1993

Effects of nicotine on brain stem mechanisms of cardiovascular control.

The role of the central nervous system in the pressor effect of nicotine is not well understood. In this study, we evaluated the cardiovascular effects of nicotine in the lower brainstem of normotensive and hypertensive rats. Microinjection of nicotine (0.012-3696 pmol/60 nl) into the nucleus of the solitary tract and area postrema of Sprague-Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) decreased blood pressure and heart rate. In contrast, administration of similar doses of nicotine within the rostral ventrolateral medulla (RVLM) evoked a long-lasting pressor and tachycardic effect. This pressor effect was completely abolished by prior microinjection of hexamethonium. In SHR the depressor and bradycardic responses in the nucleus of the solitary tract and area postrema were similar to those of normotensive animals. The pressor effect in the RVLM, however, was more pronounced in the SHR than in WKY or SD rats. In additional experiments, the changes produced by intra-RVLM administration of nicotine on renal sympathetic nerve activity, blood pressure and heart rate were evaluated before and after equidepressor intravenous doses of either clonidine, labetalol or prazosin. The prior administration of labetalol antagonized the pressor effect of nicotine in the three strains of rats (SHR, 82 +/- 6%; SD, 96 +/- 4%; WKY, 83 +/- 9%). Prazosin inhibited the nicotine pressor response by 69% in SHR, by 44% in SD and by 70% in WKY. Clonidine had no effect on nicotine response in the three groups of rats. In conclusion, nicotine administration within the RVLM increases renal sympathetic nerve activity and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A Na pump inhibitor from bovine posterior pituitary: purification, structure determination and its cardiovascular effect in rat.

We examined the hypothesis that hypothalamo-hypophysial tissue contains an endogenous Na pump inhibitor. From bovine posterior pituitary, we purified a substance which inhibits Rb uptake by human erythrocytes. This inhibitory activity was found in the eluate of 10% acetonitrile from a C18 flash column and purified by subsequent three steps of reversed-phase high-performance liquid chromatography (HPLC). Sequence analysis revealed that this substance was identical to joining peptide, one of the major products of proopiomelanocortin (POMC). This peptide had hypertensive and tachycardiac effects in spontaneously hypertensive rats (SHR) after central administration, with weak Na,K-ATPase inhibitory activity (IC50 = 0.5 mM).

Amino Acid Sequence↗
PubMed1992

Orthostatic hypotension of prolonged weightlessness: clinical models.

Orthostatic intolerance on return from space is a widely known consequence of space travel. Development of countermeasures against this problem is a major priority of the field of space physiology and medicine. The bedrest model is widely used in the investigation of this phenomenon, and has provided important data, but questions remain. In this article, we suggest that the disorders that produce chronic orthostatic hypotension have significant potential as models of microgravity-induced orthostatic intolerance. Understanding the pathophysiology of these syndromes may be useful to those involved in improving the operational aspects of manned space flight; four such syndromes and their possible relevance to space flight are described.

Autonomic Nervous System Diseases↗
PubMed1992

Adenosine as a therapeutic agent.

Adenosine, an endogenous nucleoside has been recently approved for use in the treatment of paroxysmal supraventricular tachycardia. Adenosine is nearly 100% effective in terminating tachycardia in which the atrioventricular node forms part of the reentrant circuit. Although most ventricular tachycardias are insensitive to adenosine, this substance is effective in ventricular tachycardia induced by catecholamines or exercise. An intravenous bolus dose of 6 mg is the initial dose. If no effect is noted a further bolus of 12 mg can be given. The most common side effects are dyspnea, chest pressure and facial flushing. This article reviews, in addition, some of the comparative trials with verapamil and adenosine triphosphate, some of the additional therapeutic indications, the possible mechanisms of action in cardiac tissue, and the type of purinergic receptors involved in the antiarrhythmic effects of adenosine.

Adenosine↗
PubMed1992

Chronic hypotension. In the shadow of hypertension.

Understanding the causes and treatment of chronic hypotension is of benefit to affected patients and may also shed light on the physiology and genetics of mechanisms of blood pressure control. Symptomatic hypotension (almost always with a blood pressure fall greater than or equal to 20/10 mm Hg) may reflect unrecognized medication effects or a variety of other causes. Autonomic neuropathies include those secondary to diabetes, peripheral autonomic impairment (the Bradbury-Eggleston syndrome), central autonomic impairment (the Shy-Drager syndrome), or newly described gene defects such as dopamine-beta-hydroxylase deficiency (which causes the absence of norepinephrine with an accumulation of dopamine). Baroreceptor dysfunction causes wide swings in blood pressure that are unrelated to posture, whereas a variety of stimuli (cough, micturition, or carotid sinus pressure) may precipitate paroxysmal parasympathetic activation, and sympathetic orthostatic hypotension associated with hypovolemia may occur with mitral valve prolapse or as an idiopathic condition. The differentiation of these and other causes of symptomatic hypotension may in many cases lead to beneficial therapy.

Chronic Disease↗
PubMed1991

Administration of carbamazepine in the nucleus of the solitary tract inhibits the antihypertensive effect of clonidine.

The effects of carbamazepine administration into the nucleus tractus solitarii (NTS) on central alpha 2-adrenergic cardiovascular function were studied in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Stereotaxic microinjections of carbamazepine (288 ng/60 nl) into the NTS of SHR transiently increased blood pressure, heart rate, and renal sympathetic nerve activity. These effects were followed by a modest depressor and bradycardic effect, with no change in sympathetic nerve activity. In addition, previous intra-NTS administration of carbamazepine attenuated the antihypertensive effect of the centrally acting alpha 2-adrenoceptor agonist, clonidine. Similar carbamazepine effects were observed in the WKY rats. These results suggest that some of the cardiovascular changes observed during carbamazepine treatment involve antagonism of central noradrenergic mechanisms.

Animals↗
PubMed1991

Adenosine increases sympathetic nerve traffic in humans.

BACKGROUND: Adenosine is an effective hypotensive agent in experimental animals and in anesthetized patients, producing little if any evidence of reflex sympathetic activation. In contrast, adenosine increases systolic blood pressure and heart rate in conscious subjects. To determine whether this response is related to sympathetic activation, we studied the cardiovascular and respiratory effects of adenosine in normal subjects while measuring muscle sympathetic nerve traffic through direct recordings from a peroneal nerve. METHODS AND RESULTS: Adenosine (80 micrograms/kg/min i.v.) increased heart rate (+32 +/- 3 beats/min), systolic blood pressure (+10 +/- 2 mm Hg), and minute ventilation (+7 +/- 1 l/min). This was accompanied by a dose-dependent increase in muscle sympathetic nerve activity (from 198 +/- 52 to 451 +/- 92 units/min). Adenosine also produced a small, but consistent, decrease in diastolic blood pressure (-6 +/- 3 mm Hg). Adenosine produced a greater increase in sympathetic nerve traffic (145 +/- 32% above baseline) than did nitroprusside (65 +/- 16%) at doses that resulted in equivalent decreased in diastolic blood pressure. Arterial baroreceptor unloading, therefore, could not totally explain the increase in sympathetic traffic produced by adenosine. CONCLUSIONS: Given the constellation of findings of increased ventilation and sympathetic activity, we, therefore, propose that adenosine increases sympathetic tone by activating afferent nerves, including arterial chemoreceptors. Contrary to the known inhibitory actions of adenosine on central and peripheral efferent systems, this and other reports suggest that adenosine-induced activation of afferent nerves, leading to sympathetic activation, may be a more widespread phenomenon than previously recognized.

Adenosine↗
PubMed1991

Cardiovascular excitatory effects of adenosine in the nucleus of the solitary tract.

Adenosine is an inhibitory neuromodulator in several brain regions. In the nucleus tractus solitarius (NTS), however, adenosine exerts excitatory cardiovascular effects. The purpose of the present study was to elucidate the involvement of other endogenous mechanisms that could contribute to the final hemodynamic response to adenosine in this nucleus. In normotensive Sprague-Dawley rats, intra-NTS microinjection of adenosine (2.3 nmol/60 nl) decreased blood pressure and heart rate. These effects were blocked by prior administration of the specific adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol) and by the two glutamate receptor antagonists kynurenic acid and glutamic diethylester. The specificity of the adenosine-glutamate interaction in the NTS was demonstrated with adrenergic and angiotensin receptor antagonists that did not affect the adenosine response and by experiments with glutamate receptor antagonists that did not affect nicotine actions in the NTS. Furthermore, an increase in glutamate levels was demonstrated during perfusion of adenosine through a microdialysis probe in the NTS of anesthetized rabbits. These findings indicate that adenosine increases the release of glutamate in the NTS and, thus, are at variance with the concept of a "universal" inhibitory effect of adenosine in the central nervous system.

Adenosine↗
PubMed1990

Effects of caffeine on baroreflex activity in humans.

The effects of caffeine or placebo on blood pressure, heart rate, and baroreflex activation (elicited by phenylephrine) were studied on young normotensive volunteers after a 7-day caffeine-free period. Subjects received oral doses of either 250 mg caffeine (n = 6) or placebo (n = 4), and hemodynamic changes were studied at 0, 30, 60, 120, and 180 minutes after drug administration. Thirty minutes after the caffeine dose, blood pressure had risen from 127 +/- 8/57 +/- 4 mm Hg to 136 +/- 3/68 +/- 5 mm Hg, heart rate was unchanged, and the baroreflex slope had decreased from 31 +/- 7 msec/mm Hg to 11.6 +/- 2 msec/mm Hg. Baroreflex sensitivity remained inhibited for the rest of the single-dose experimental period. In contrast, no significant changes were observed after either long-term caffeine ingestion in the same group or in the placebo group during the single- or multiple-dose study. These findings indicate that single but not multiple caffeine administration inhibits baroreflex activation in normotensive volunteers and this could contribute to the acute hemodynamic effects of caffeine.

Administration, Oral↗
PubMed1990

Cardiovascular effects of microinjection of angiotensin II in the brainstem of renal hypertensive rats.

The cardiovascular effects of microinjection of angiotensin II (AII) into the area postrema (AP), nucleus of the solitary tract (NTS) and rostroventrolateral medulla were studied in urethane anesthetized sham-normotensive (NT) and two-kidney, one-clip renal hypertensive rats. Microinjection of AII (2-2000 ng) in the AP of renal hypertensive rats elicited a dose-dependent decrease in blood pressure, heart rate and renal sympathetic nerve activity. Similar effects were observed in the NTS. In the NT rats, low doses of AII (2 and 20 ng), either in the AP or NTS, were also depressor. High doses of AII (200-2000 ng) were needed to observe a modest pressor effect in the NT animals. A decrease in heart rate and renal sympathetic activity was observed with the pressor effect. The AII-antagonist, [Sar1,Val5,Ala8]-AII, into the NTS or AP increased blood pressure and heart rate and inhibited the cardiovascular effects of low doses of AII in both group of rats. In contrast, [Sar1,Val5,Ala8]AII did not affect the pressor action of high doses of AII in the NT group. While the microinjection of AII into the rostroventrolateral medulla did not produce any significant cardiovascular effect in the renal hypertensive group, it resulted in a modest pressor effect in the NT rats. These results indicate that acute activation of AII receptors in the AP or NTS does not contribute to the pressor effect of AII in renal hypertensive rats.

Angiotensin II↗
PubMed1989

Modulatory effects of adenosine on baroreflex activation in the brainstem of normotensive rats.

The effects of the adenosine antagonists, 1,3-dipropyl-8-p-sulphenylxanthine (DPSPX) and caffeine, on baroreflex activity were tested in normotensive Sprague-Dawley rats. The microinjection of DPSPX (0.92 nmol) into the nucleus tractus solitarii (NTS) of urethane-anesthetized animals did not modify basal blood pressure or heart rate but inhibited the reflex bradycardia elicited by phenylephrine. Similar inhibitory effects on baroreflex activation were observed after intracisternal administration of caffeine to conscious or anesthetized animals. These results suggest that central endogenous adenosine is involved in the medullary regulation of blood pressure and that adenosine antagonists such as caffeine can inhibit baroreflex activation.

Adenosine↗