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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac taurine levels are elevated in hypertension and congestive heart failure. A possible mechanism for this increase in taurine is an alteration of its uptake. We sought to identify and characterize a carrier-mediated transport system for taurine in the mammalian myocardium utilizing the fetal mouse heart in organ culture. Hearts from fetuses of 16-19 days gestational age used in these studies had an endogenous taurine content of 14.1+/-0.5 nmol/mg tissue. The uptake of [(3)H]taurine was linear for up to 8 h. Taurine was accumulated against a concentration gradient as demonstrated by a net increase in taurine concentration when hearts were incubated in 0.5 mM taurine. [(3)H]Taurine uptake was saturable, K(m) = 0.44 mM, temperature dependent, and required sodium. The close structural analogues, hypotaurine and beta-alanine, reduced [(3)H]taurine uptake by 87% when present in 100-fold excess. The alpha-amino acids alanine, alpha-aminoisobutyric acid, glycine, leucine, and threonine did not inhibit uptake. Other taurine analogues tested were guanidinotaurine, guanidinopropionic acid, gamma-aminobutyric acid, 2-aminoethane phosphonic acid, aminomethane sulfonic acid, 3-aminopropane sulfonic acid, N-acetyltaurine, and isethionic acid. We conclude that a carrier-mediated transport system for taurine exists in the fetal mouse heart based on the demonstration of (a) temperature dependence, (b) saturability, and (c) structural selectivity of the uptake process. Transport was demonstrated to be mediated by a beta-amino acid uptake system. In addition, taurine uptake was observed to be sodium dependent, energy dependent, and capable of accumulating taurine against a concentration gradient.
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PMID:Characterization of a carrier-mediated transport system for taurine in the fetal mouse heart in vitro. 65 83

There is compelling evidence for the participation of excitatory and inhibitory amino acids in the neural regulation of blood pressure in the normotensive rat. This is most clearly evident in the neural pathways which form the baroreceptor reflex arc. Excitatory amino acids are contained in baroreceptor afferents, neurons in the nucleus tractus solitarius (NTS) and neurons in the rostral ventrolateral medulla (RVLM). Inhibitory neurons in the caudal ventrolateral medulla (CVLM) contain gamma-aminobutyric acid. Electrophysiological and pharmacological evidence indicates that amino acid neurotransmitters are critically important to the normal function of these integrative sites in the baroreceptor reflex. Spontaneously hypertensive rats (SHR) differ from Wistar Kyoto (WKY) controls in their responses to stimulation, inhibition or lesions of neurons in the baroreceptor arc. One week after baroreceptor denervation, blood pressure is elevated in WKY but not in SHR. Stimulation of the CVLM results in a greater fall in pressure in SHR than WKY, whereas injection of tetrodotoxin into the CVLM results in a smaller increase in pressure in SHR. Blockade of glutamate receptors in the spinal cord attenuates the response to stimulation of the RVLM in both SHR and WKY, but reduces resting blood pressure in SHR only. These experiments suggest that altered activity in amino acid pathways contributes to the pathogenesis of hypertension in SHR.
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PMID:Amino acid neurotransmitters in hypertension. 135 37

The influence of chronically administered propranolol on the functional state of the gamma-aminobutyric acid-ergic (GABAergic) system in spontaneously hypertensive rats was studied and compared with the effect of dihydralazine. GABA content, synthesis and turnover rate in selected brain areas were assessed. Hypotensive activity of propranolol and dihydralazine after injection of GABA antagonist pictrotoxin was examined in acute experiment. Prolonged administration of propranolol increased GABA content, synthesis and turnover rate in the hypothalamus and the pons-medulla. After chronic injections of dihydralazine there was no change in GABA indices. Antihypertensive activity of dihydralazine in picrotoxin-treated animals remained unchanged. On the contrary, picrotoxin suppressed the propranolol-induced decrease in blood pressure. Our results indicate that propranolol increases GABAergic system activity. Therefore, we conclude that down-regulation of the GABAergic system in hypertension may be compensated by the regulatory action of propranolol.
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PMID:Increased activity of the GABAergic system in selected brain areas after chronic propranolol treatment in spontaneously hypertensive rats. 151 Jun 97

Previous studies have demonstrated that bupivacaine administered directly into the central nervous system (CNS) is capable of producing signs of bupivacaine cardiovascular toxicity. To investigate the mechanisms by which bupivacaine may act within the CNS to produce cardiovascular toxicity, we studied four groups of halothane-anesthetized rabbits in which infusion of intracerebroventricular (icv) bupivacaine or intravenous (iv) phenylephrine resulted in dysrhythmias and hypertension. In group 1 (n = 5), icv bupivacaine (500 +/- 79 micrograms [mean +/- SEM]) produced dysrhythmias lasting 73 +/- 13 min, whereas icv saline caused no dysrhythmias or hypertension. In group 2 (n = 9), icv bupivacaine-induced hypertension and dysrhythmias were abolished by icv midazolam in 4.4 +/- 0.6 min, and when dysrhythmias and hypertension recurred (22 +/- 0.9 min), hexamethonium (10 mg/kg iv) promptly terminated dysrhythmias and hypertension (14 +/- 1 s). In group 3 (n = 10), icv bupivacaine-induced dysrhythmias and hypertension were not affected by increasing the inspired halothane concentration from 0.8 to 1.6%. In group 4 (n = 6), iv phenylephrine-induced dysrhythmias and hypertension were not affected by icv midazolam. These results suggest that icv bupivacaine produces dysrhythmias and hypertension by increasing autonomic nervous system (ANS) outflow from the brain stem. The finding that peripheral autonomic blockade by hexamethonium rapidly terminated dysrhythmias and hypertension supports this mechanism. We speculate that icv bupivacaine produces an increase in autonomic outflow by blockade of the inhibitory gamma-aminobutyric acid (GABA) neurons that are known to be the principal tonic inhibitors of the ANS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits. 167 Sep 15

To determine whether chronic central gamma-aminobutyric acid (GABA) stimulation would attenuate development of hypertension, tail-cuff systolic pressures were measured in male spontaneously hypertensive rats (SHR) treated with either an inhibitor of GABA breakdown (valproate, VPA), or a GABA-receptor agonist (muscimol). When VPA was injected intraperitoneally (i.p.) daily for 4 weeks, tail-cuff systolic pressures were decreased during the last 2 weeks. On the other hand, continuous infusion of muscimol into the lateral cerebral ventricle for 14 days using an osmotic minipump decreased systolic pressures throughout the 10-day observation period. During terminal experiments under urethane anesthesia, pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were reduced in VPA- or muscimol-treated SHR. Pressor responses to intravenously (i.v.) injected norepinephrine (NE) were unaltered by either treatment, indicating that diminished pressor responsiveness to hypothalamic stimulation was not due to diminished cardiovascular reactivity. Regardless of either VPA acid or muscimol treatment, basal blood pressure (BP), heart rate (HR), and responses to hypothalamic stimulation were lower in normotensive Wistar-Kyoto controls (WKY) than in SHR. In addition, chronic treatment with either drug had weaker hypotensive and hypothalamic depressant effects in WKY than in SHR. Our results suggest that in SHR the central GABAergic system is impaired and that chronic treatment with GABAergic stimulants can attenuate development of spontaneous hypertension by reducing hypothalamic overactivity.
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PMID:Chronic central GABAergic stimulation attenuates hypothalamic hyperactivity and development of spontaneous hypertension in rats. 169 29

The circulatory effects of intracisternal injections of amino acids were investigated in conscious normotensive control rats (NCR) and in two-kidney, one-clip renovascular hypertensive rats (RHR). Arterial pressure was measured with an indwelling catheter connected to a pressure transducer. Heart rate was counted from the arterial pulse. The intracisternal injection of glycine, gamma-aminobutyric acid (GABA), taurine, serine, alanine, and sarcosine decreased blood pressure by an average of 16-30 mmHg in NCR and by an average of 32-55 mmHg in RHR. Both absolute and percent changes of depressor effects by GABA, taurine, serine, and alanine were larger in RHR than in NCR. All these amino acids also showed similar bradycardiac effects in both NCR and RHR, when compared in absolute values. The percent change of bradycardia induced by taurine and sarcosine was larger in RHR than in NCR. However, the degree of bradycardia by serine was larger in NCR than in RHR. These results suggest that serine, alanine, and sarcosine in addition to glycine, GABA, and taurine, play important roles in blood pressure control in conscious normotensive rats via central neural mechanisms and that the hypertension in renovascular hypertensive rats may involve a central abnormality.
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PMID:Central depressor effects of amino acids in conscious normotensive and two-kidney, one-clip renovascular hypertensive rats. 180 55

The present study was undertaken to determine whether gamma-aminobutyric acid in the paraventricular nucleus contributes to the regulation of cardiovascular function. Blood pressure and heart rate were recorded and plasma catecholamines were measured in conscious rats receiving microinfusions of either artificial cerebrospinal fluid or a gamma-aminobutyric acid antagonist, bicuculline methiodide, bilaterally into the paraventricular nucleus. Artificial cerebrospinal fluid had no effect on any of the recorded variables. In contrast, infusion of bicuculline into the region of the paraventricular nucleus produced increases in blood pressure (20 +/- 2 mm Hg), heart rate (110 +/- 11 beats/min), and plasma concentrations of norepinephrine (640 +/- 107 pg/ml) and epinephrine (1,266 +/- 267 pg/ml). Pretreatment with a ganglionic blocking agent abolished both the blood pressure (-1 +/- 2 mm Hg) and heart rate (5 +/- 18 beats/min) effects. Bilateral adrenal medullectomy reduced the changes in plasma norepinephrine concentrations (81 +/- 14 pg/ml) significantly and abolished the changes in plasma epinephrine concentrations (5 +/- 4 pg/ml). Conversely, adrenal medullectomy reduced the pressor effects (18 +/- 2 mm Hg) only slightly while the heart rate responses were attenuated (42 +/- 9 beats/min) by approximately 50%. These results suggest that an endogenous gamma-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus.
Hypertension 1991 Jul
PMID:Cardiovascular responses to bicuculline in the paraventricular nucleus of the rat. 186 Jul 11

Reports suggested that the predominant site of action for the antihypertensive effects of clonidine is the rostral ventrolateral medulla (RVL), the presumed tonic vasomotor center. This study examined whether clonidine directly interacts with nerve terminal alpha 2-adrenergic receptors in the RVL to inhibit the release of sympathoexcitatory transmitters like glutamate (Glu) and aspartate (Asp), and/or facilitate the release of sympathoinhibitory transmitters like gamma-aminobutyric acid (GABA). Release of GABA and Glu was measured from synaptosomes prepared from the rostral ventral medulla of spontaneously hypertensive rats (SHR), a genetic model of hypertension, and normotensive Wistar-Kyoto rats (WKY). Quantification of neurotransmitter release was performed by high-performance liquid chromatography. Depolarization with 35 mM K+ significantly increased by 58-110% the release of GABA, Glu and Asp; however, no strain differences were observed. In contrast, spontaneous release of GABA and Asp was significantly lower in SHR than that of WKY (-36 and -41%, respectively); this effect was not observed for Glu. Clonidine (1 and 10 microM) enhanced the spontaneous release of GABA (+44%), Asp (+50%) and Glu (+70%) in SHR, but not WKY; this effect was prevented by yohimbine (1 microM). These data, together with previous findings, support the presence of facilitory alpha 2-adrenergic receptors on nerve terminals of GABAergic, glutamatergic and aspartatergic neurons in the rostral ventral medulla. These findings also suggest the existence of another inhibitory transmitter that may mediate the actions of clonidine to decrease sympathetic outflow from the RVL.
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PMID:Evidence for clonidine presynaptically modulating amino acid release in the rostral ventral medulla: role in hypertension. 198 40

A placebo may be a pharmacologically active or an inert substance, a procedure, or a patient-doctor interview. Placebos work best in symptoms or disease which vary over time and between patients. The placebo works best in behaviour disorders, somatic autonomic disorders like pain, and neurohumoral disorders like hypertension. However, placebo action is incompletely defined in its molecular pharmacology. The endogenous brain systems of opioid, antiopioid, and gamma-aminobutyric acid polypeptide transmitters and neuronal receptors account in part for placebo analgesia. Non-painful stress may be mediated through other neurohumoral systems. A separate neural system might control these subsystems. Confidence based on the doctor's empathy commonly evokes the placebo effect. How the symbolic input of thought or emotion is translated into neuronal events is unknown. Double-masked 'controlled' clinical trials use placebo to reduce bias; overuse of placebo here may harm some patients. Oral placebos for routine use include thiamine at low dose. Potent drugs like glucocorticoids cannot be justified as placebo in mild disease or non-disease. Both patient and doctor are usually unaware of the placebo effect during interviews. Doctors may increase placebo efficacy by improving interpersonal skills.
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PMID:Magic or medicine? Clinical pharmacological basis of placebo medication. 202 61

The role of Ca2(+)-calmodulin-dependent protein kinase II (CaM kinase II) in the central nervous system has been studied with special reference to the effect of CaM kinase II inhibitor on gamma-aminobutyric acid (GABA) release. We have used two different selective inhibitors of Ca2(+)-calmodulin-dependent enzymes such as a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), and a newly synthesized selective inhibitor of CaM kinase II, 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpipe raz ine (KN-62). N-[1-[P-(5-Isoquinolinesulfonyl)benzyl]-2-(4- phenylpiperazinyl)ethyl]-5-isoquinolinesulfonamide (KN-04), a derivative of KN-62, which has a much lower inhibitory activity on the enzyme, was also synthesized for use as a control. Although i.v. injection of the drugs did not produce any effect, infusion of W-7 or KN-62 into the 4th ventricle produce any effect, infusion of W-7 or KN-62 into the 4th ventricle of the rat caused hypertension and tachycardia, associated with the diminished rate of GABA release in cerebrospinal fluid. The ability of KN-62 to produce these effects was more potent than that of W-7. Intracisternal infusion of KN-04 influenced neither systemic blood pressure nor GABA release at the concentration up to 100 microM. The same order of potencies of three agents (KN-62 greater than W-7 much greater than KN-04) has been obtained in their effects on either in vitro CaM kinase II activity, the in vivo autonomic nervous system or the rate of GABA release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a new Ca2(+)-calmodulin-dependent protein kinase II inhibitor on GABA release in cerebrospinal fluid of the rat. 238 87


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