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

Angiotensin II type 1 (AT(1)) receptors are located on pressor neurons in the rostral ventrolateral medulla, and their activation results in an increase in arterial pressure. However, the normal role of these AT(1) receptors in cardiovascular regulation is unknown. In this study, we tested the hypothesis that these receptors mediate synaptic excitation of rostral ventrolateral medullary pressor neurons in response to activation of the hypothalamic paraventricular nucleus. In anesthetized rats, microinjections of the gamma-aminobutyric acid receptor antagonist bicuculline were made into the paraventricular nucleus; this injection causes activation of the nucleus as a consequence of disinhibition. The pressor and sympathoexcitatory responses evoked by paraventricular nucleus activation were significantly reduced (by approximately 40% to 50%) after microinjection of the specific AT(1) receptor antagonists losartan or L-158,809 into the rostral ventrolateral medulla on the ipsilateral, but not contralateral, side. These responses were reduced to a similar degree after microinjections of the neuroinhibitory compound muscimol into the ipsilateral, but not contralateral, rostral ventrolateral medulla. However, bilateral microinjections of the glutamate receptor antagonist kynurenic acid into the rostral ventrolateral medulla had no effect on the responses evoked from the paraventricular nucleus. Conversely, bilateral microinjections of kynurenic acid into the rostral ventrolateral medulla virtually abolished the somatosympathoexcitatory reflex, whereas bilateral microinjections of losartan or L-158,809 had no effect on this reflex. The results indicate that excitatory synaptic inputs to pressor neurons in the rostral ventrolateral medulla arising from activation of the paraventricular nucleus are mediated predominantly by AT(1) receptors.
Hypertension 1999 Dec
PMID:AT(1) receptors mediate excitatory inputs to rostral ventrolateral medulla pressor neurons from hypothalamus. 1060 Nov 34

NO is known to be involved in the peripheral and central regulation of the cardiovascular function. It plays a neuromodulatory role via a direct action on presynaptic nerve terminals, stimulating the release of gamma-aminobutyric acid, glutamate, and norepinephrine. Our aim was to study the possible role of NO in the cardiovascular effects of the central antihypertensive drugs clonidine, rilmenidine, and alpha-methyl-norepinephrine (alpha-MNA). Sites and mechanisms of the hypotensive action of these drugs were different; clonidine and rilmenidine acted on imidazoline receptors in the nucleus reticularis lateralis, whereas alpha-MNA acted upon alpha(2)-adrenoceptors in the nucleus tractus solitarius. The influence of N:(G)-nitro-L-arginine, an NO synthase inhibitor, on the central hypotensive effects of these drugs was investigated in pentobarbital-anesthetized rabbits. The intracisternal (IC) administration of alpha-MNA (30 microg/kg) induced hypotension (79+/-2 versus 103+/-4 mm Hg) and bradycardia (222+/-8 versus 278+/-4 bpm) (P:<0.05) (n=5). Clonidine (0.07 microg/kg IC) also induced hypotension (69+/-5 versus 99+/-4 mm Hg) and bradycardia (266+/-7 versus 306+/-10 bpm) (P:<0.05) (n=5). In addition to clonidine, rilmenidine (1 microg/kg IC) induced hypotension (64+/-4 versus 97+/-4 mm Hg) and bradycardia (264+/-11 versus 310+/-4 bpm) (P:<0.05) (n=5). Pretreatment with N:(G)-nitro-L-arginine (900 microg/kg IC) completely prevented the hypotensive effect of alpha-MNA but influenced the cardiovascular effects of neither clonidine nor rilmenidine. These results confirm that imidazoline drugs, such as clonidine, rilmenidine, and the catecholamine alpha(2)-adrenoceptor agonist alpha-MNA, have distinct mechanisms of action.
Hypertension 2001 Feb
PMID:Nitric oxide and central antihypertensive drugs: one more difference between catecholamines and imidazolines. 1123 Feb 79

The goal of this study was to determine whether gamma-aminobutyric acid (GABA)ergic transmission and GABA binding are altered in chronic renal-wrap hypertension. Three groups of hypertensive and sham-operated rats were prepared for separate protocols. Four weeks later, the animals were prepared with femoral artery catheters for the measurement of mean arterial pressure. In all groups, blood pressure was significantly higher in the renal-wrapped animals. In the first study, bilateral microinjection of the GABA-A antagonist, bicuculline (50 pmol/site), into the paraventricular nucleus of the hypothalamus (PVN) caused a greater increase in arterial pressure (21.9+/-1.4 versus 16.7+/-1.8 mm Hg, P<0.05) and heart rate (135+/-15 versus 98+/-12 bpm, P=0.064) in hypertensive rats. [(3)H]Flunitrazepam was used to measure binding to the GABA-A receptor. Magnocellular neurons and the adjacent medial parvicellular neurons had more intense binding compared with the remainder of the PVN. B(max) was greater for the higher density binding area; the K(d) value was less in the high-density region. There were no differences in these parameters between normotensive and hypertensive animals. Competitive reverse transcription-polymerase chain reaction was used to measure the expression of mRNA for the alpha(1) subunit of the GABA-A receptor. No difference was observed in the mRNA between renal-wrapped and sham-operated rats. In summary, inhibition of GABA-A receptors in the PVN is augmented in the chronic phase of hypertension and is unrelated to a change in the expression of the number or affinity to the receptor. These findings suggest that the greater GABAergic activity is the result of an increase in GABA release in the PVN in chronic renal-wrap hypertension.
Hypertension 2001 Feb
PMID:gamma-Aminobutyric acid (GABA)--A function and binding in the paraventricular nucleus of the hypothalamus in chronic renal-wrap hypertension. 1123 Mar 44

The increase in mean arterial pressure evoked by injection of the gamma-aminobutyric acid (GABA)(B) agonist baclofen into the nucleus tractus solitarius (NTS) is greater in spontaneously hypertensive rats and renal wrap chronically hypertensive (CHT) rats compared with normotensive (NT) controls. We report here that the baclofen-induced pressor response (BIPR) is enhanced after acute hypertension (AHT) of only 30 minutes. Sprague-Dawley rats were anesthetized with Inactin, paralyzed, and artificially ventilated. As we previously reported, after unilateral electrolytic ablation of the NTS, microinjection of 40 pmol baclofen into the contralateral NTS of NT rats resulted in a BIPR of 22+/-1 mm Hg (n=12). During the infusion of phenylephrine for 30 minutes (AHT), the BIPR was 39+/-5 mm Hg (n=10), significantly greater than the response in NT rats (P<0.01) and no different from the response in CHT rats (39+/-5 mm Hg, n=7). Baclofen has both presynaptic and postsynaptic effects. To eliminate the presynaptic component of the baclofen response, sinoaortic denervation (SAD) was performed before the microinjections. The magnitude of the BIPR was 12+/-1 mm Hg in NT-SAD rats (n=8), 12+/-1 mm Hg in AHT-SAD rats (n=12), and 20+/-3 mm Hg in CHT-SAD rats (n=7). The BIPR is enhanced in both CHT and AHT rats. It appears that the increase in baroreceptor afferent input to NTS during phenylephrine-induced AHT provides a greater substrate for presynaptic inhibition by baclofen because the postsynaptic component of the baclofen response is the same in NT-SAD and AHT-SAD. The enhanced BIPR in CHT rats appears to be associated with an enhancement of both the presynaptic and postsynaptic components of the response.
Hypertension 2001 Feb
PMID:gamma-Aminobutyric acid(B) receptor-mediated responses in the nucleus tractus solitarius are altered in acute and chronic hypertension. 1123 Mar 45

References to the word ecstasy in popular culture can mean different things to different individuals. The most common form of ecstasy (3,4-methylenedioxymethamphetamine [MDMA]), is an amphetamine with some hallucinogenic properties at high doses. It is directly neurotoxic to the human brain and has been linked to a number of deaths worldwide. Deaths result from hyperthermia, hyponatremia, or cerebral edema. A naturally occurring metabolite of gamma-aminobutyric acid, gammahydroxybutyrate (GHB) is a potent central nervous system depressant. Although GHB is a Schedule I drug, analogs remain widely available for consumption. Acute intoxication with GHB or its analogs leads to coma and respiratory depression. Chronic use of GHB or its analogs is associated with a withdrawal syndrome characterized by autonomic excitation. Herbal ecstasy refers to ephedrine-containing preparations. Acute and chronic overdoses of herbal ecstasy have been linked to hypertension, tachydysrythmias, myocardial infarctions, cerebrovascular accidents, and deaths. There is no regulation of the ephedrine content of available herbal ecstasy products.
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PMID:The many faces of ecstasy. 1131 61

Spinal cord injury (SCI) leads to plastic changes in organization that impact significantly on central nervous control of arterial pressure. SCI causes hypotension and autonomic dysreflexia, an episodic hypertension induced by spinal reflexes. Sympathetic preganglionic neurons (SPNs) respond to SCI by retracting and then regrowing their dendrites within 2 weeks of injury. We examined changes in synaptic input to SPNs during this time by comparing the density and amino acid content of synaptic input to choline acetyltransferase (ChAT)-immunoreactive SPNs in the eighth thoracic spinal cord segment (T8) in unoperated rats and in rats at 3 days or at 14 days after spinal cord transection at T4. Postembedding immunogold labeling demonstrated immunoreactivity for glutamate or gamma-aminobutyric acid (GABA) within presynaptic profiles. We counted the number of presynaptic inputs to measured lengths of SPN somatic and dendritic membrane and identified the amino acid in each input. We also assessed gross changes in the morphology of SPNs using retrograde labeling with cholera toxin B and light microscopy to determine the structural changes that were present at the time of evaluation of synaptic density and amino acid content. At 3 days after SCI, we found that retrogradely labeled SPNs had shrunken somata and greatly shortened dendrites. Synaptic density (inputs per 10-microm membrane) decreased on ChAT-immunoreactive somata by 34% but increased on dendrites by 66%. Almost half of the inputs to SPNs lacked amino acids. By 14 days, the density of synaptic inputs to dendrites and somata decreased by 50% and 70%, respectively, concurrent with dendrite regrowth. The proportion of glutamatergic inputs to SPNs in spinal cord-transected rats ( approximately 40%) was less than that in unoperated rats, whereas the GABAergic proportion (60-68%) increased. In summary, SPNs participate in vasomotor control after SCI despite profound denervation. An altered balance of excitatory and inhibitory inputs may explain injury-induced hypotension.
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PMID:Changes in synaptic inputs to sympathetic preganglionic neurons after spinal cord injury. 1139 43

The tachycardic, pressor, and renal sympathoexcitatory responses produced by administration of the gamma-aminobutyric acid antagonist bicuculline into the paraventricular nucleus of the rat are attenuated by the administration of losartan, an angiotensin II type 1 receptor antagonist, into the ipsilateral rostroventrolateral medulla. Therefore, excitatory synaptic inputs to pressor neurons in the rostroventrolateral medulla that arise from activation of the paraventricular nucleus are mediated predominantly by the action of angiotensin II on angiotensin II type 1 receptors. To examine whether such responses are influenced by physiological changes in the activity of the renin-angiotensin system, we measured heart rate, arterial pressure, and renal sympathetic nerve activity responses to the administration of bicuculline in the paraventricular nucleus in normal rats that were fed low-, normal-, and high-sodium diets and in rats with congestive heart failure. The rank order of both plasma renin activity and renal sympathoexcitatory responses was congestive heart failure>low-sodium diet>normal-sodium diet>high-sodium diet. The rank order of pressor and tachycardic responses exhibited a similar trend, but the differences between the groups were smaller and not statistically significant. The results indicate that the renal sympathoexcitatory responses to activation of the paraventricular nucleus are modulated by physiological alterations in the activity of the renin-angiotensin system.
Hypertension 2001 Aug
PMID:Effect of dietary sodium intake on the responses to bicuculline in the paraventricular nucleus of rats. 1150 75

The abuse of methylenedioxymethamphetamine (MDMA), flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate (GHB) is discussed. Club drugs are chemical substances used recreationally in social settings. Use is increasingly frequent among young people, especially during all-night dance parties. All four agents have been classified as controlled substances. MDMA ("ecstasy") is available as a tablet, a capsule, and a powder; formulations may contain many adulterants. MDMA increases the release of neurotransmitters. The desired effects are euphoria, a feeling of intimacy, altered visual perception, enhanced libido, and increased energy. The most common adverse effects are agitation, anxiety, tachycardia, and hypertension. More serious adverse effects include arrhythmias, hyperthermia, and rhabdomyolysis. Flunitrazepam is a potent benzodiazepine. At higher doses, the drug can cause lack of muscle control and loss of consciousness. Other adverse effects are hypotension, dizziness, confusion, and occasional aggression. Ketamine is a dissociative anesthetic used primarily in veterinary practice. It may be injected, swallowed, snorted, or smoked. Like phencyclidine, ketamine interacts with the N-methyl-D-aspartate channel. Analgesic effects occur at lower doses and amnestic effects at higher doses. Cardiovascular and respiratory toxicity may occur, as well as confusion, hostility, and delirium. GHB, a naturally occurring fatty acid derivative of gamma-aminobutyric acid, was introduced as a dietary supplement. Increasing doses progressively produce amnesia, drowsiness, dizziness, euphoria, seizures, coma, and death. Flunitrazepam, ketamine, and GHB have been used to facilitate sexual assault. Supportive care is indicated for most cases of club drug intoxication. The increasing abuse of MDMA, flunitrazepam, ketamine hydrochloride, and GHB, particularly by young people in social settings such as clubs, should put health care professionals on guard to recognize and manage serious reactions.
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PMID:Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. 1206 92

To examine the role of nitric oxide in the brain stem on cardiovascular response in vivo, we have developed and applied a technique of endothelial nitric oxide synthase gene transfer into the nucleus tractus solitarii or the rostral ventrolateral medulla of rats in vivo. The blood pressure and heart rate were monitored using a radiotelemetry system in the conscious state. As a marker of sympathetic nerve activity, we measured 24-h urinary norepinephrine excretion. We found that overexpression of endothelial nitric oxide synthase in the nucleus tractus solitarii as well as in the rostral ventrolateral medulla causes hypotension and bradycardia via a decrease in sympathetic nerve activity. Furthermore, in the case of the local increases in nitric oxide in the rostral ventrolateral medulla, we suggest that this effect is mediated by an increase in gamma-aminobutyric acid. Moreover, in the stroke-prone spontaneously hypertensive rat, the increase in nitric oxide production evoked by the overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla caused greater depressor and sympatho-inhibitory responses than in normotensive Wistar-Kyoto rats, suggesting that an abnormality of the L-arginine-nitric oxide pathway may be involved in the central mechanisms of hypertension in this model.
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PMID:Effect of overproduction of nitric oxide in the brain stem on the cardiovascular response in conscious rats. 1268 8

This study aimed to determine the antihypertensive and metabolic effects of an aqueous extract of Monascus purpureus M9011 on fructose-induced hypertensive rats. After dietary feeding of fructose for 2 weeks, the rats exhibited significantly higher systolic blood pressure (SBP), mean arterial pressure (MAP), and plasma insulin and triglyceride levels, but lower insulin sensitivity than those in control rats on regular diet. The intragastric loading of fructose-fed rats with M9011 containing gamma-aminobutyric acid (GABA, 1 mg.kg(-)(1).day(-)(1)) prevented the development of fructose-induced hypertension. After fructose-induced hypertension had been established, intragastric loading of M9011 reversed the elevated blood pressure to normal level. Administration of pure GABA at the same dose as that contained in M9011 failed to prevent or reverse hypertension due to fructose consumption. Chronic M9011 treatment significantly suppressed the fructose-induced elevation in total cholesterol levels and enhanced the recovery of high-density lipoprotein cholesterol/total cholesterol ratio. However, M9011 treatment did not alter insulin sensitivity or the plasma levels of insulin, glucose, and triglyceride in fructose-fed and control rats. The present results suggest that M9011 is a novel, potent, food-based antihypertensive agent with the capability to improve long-term control of cholesterol metabolism in rats and may be of importance in clinical application for the hypertensive diabetic population.
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PMID:Aqueous extract of Monascus purpureus M9011 prevents and reverses fructose-induced hypertension in rats. 1282 28


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