Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most important central autonomic pathways in the control of arterial blood pressure are the baroreceptor reflex pathway and descending pathways from the hypothalamus. Central neurotransmitters in these pathways are L-glutamate, substance P, norepinephrine (NE), gamma-aminobutyric acid, epinephrine, neuropeptide Y, and acetylcholine. At peripheral autonomic neurovascular junctions, there are prejunctional alpha 2- and dopamine-2 receptors, which inhibit NE release, and beta- and serotonin receptors, which stimulate NE release. Postjunctional alpha 1-receptors open sodium channels, open calcium channels via phosphoinositol release, and release intracytoplasmic calcium. Postjunctional alpha 2-receptors, which are extrasynaptic, inhibit adenylate cyclase and also open calcium channels. In animal models of hypertension, changes in alpha-receptor density have been reported. In spontaneously hypertensive rats, increased renal beta- and alpha 2-receptors, respectively, may enhance renin release and cause sodium and water retention. In experimental (renovascular) hypertension, vascular postsynaptic (vasoconstrictor) alpha 1- and alpha 2-receptors are increased. In both models of hypertension, beta-receptors are down-regulated. Selective alpha 1-antagonists, such as indoramin and prazosin, decrease arterial blood pressure by postsynaptic alpha 1-blockade; alpha 2-receptor inhibition of NE release is unaffected so that there is no beta-receptor-mediated tachycardia.
 ...
PMID:Alpha-adrenoreceptors in hypertension. 242 93

Effects of oral administration of NC-1100 on the metabolism of neuroactive amino acids in rat brain were studied using stroke-prone spontaneously hypertensive (SHR-SP) and Wistar Kyoto rats. The repeated administration of NC-1100 induced a significant increase of gamma-aminobutyric acid (GABA) content in the cerebellum and medulla oblongata of SHR-SP. The decrease of aspartic acid contents in the cerebellum and medulla oblongata of SHR-SP was also noted following NC-1100 administration. Although the activity of L-glutamic acid decarboxylase did not change in these cerebral areas, the activity of GABA-transaminase:succinic semialdehyde dehydrogenase was found to be significantly reduced in the cerebellum of SHR-SP following the repeated administration of NC-1100. The turnover rate of GABA was also significantly reduced in the cerebellum and medulla oblongata of SHR-SP. It was also found that the spontaneous release of preloaded [3H]GABA from cerebral cortical slices was significantly retarded by the continuous oral administration of NC-1100. These results suggest that NC-1100 may be a drug inducing the increase of GABA in the cerebellum and medulla oblongata following continuous administration, especially in animals having hypertension associated cerebrovascular disorders such as SHR-SP.
 ...
PMID:Effect of NC-1100 [1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl) ethanol dihydrochloride] on gamma-aminobutyric acid (GABA) metabolism in rat brain: analysis using stroke-prone spontaneously hypertensive rat. 277 51

The past 15 years have been witness to a remarkable growth in knowledge regarding the modulation of "sympathetic traffic" to neuroeffector organs, including vascular tissue. The release of norepinephrine from peripheral sympathetic neurons is now known to be under both negative and positive feedback control. Norepinephrine, when released from peripheral neurons, acts on presynaptic alpha 2-receptors to inhibit further neurotransmission. Vascular postsynaptic alpha 2-receptors, sensitive to circulating catecholamines, subserve vasoconstriction. The antihypertensive agents clonidine, guanabenz and guanfacin likely reduce blood pressure by acting centrally on alpha 2 postsynaptic neurons to limit sympathetic transmission to blood vessels. Clonidine can produce venoconstriction and thereby improve orthostatic hypotension by activating venous alpha 2-receptors. Additional presynaptic dopaminergic receptors (DA2), muscarinic receptors (acetylcholine), opioid receptors, prostaglandin receptors, adenosine receptors (A1) and histamine (H2) receptors are present on sympathetic nerve membranes and, when engaged with the appropriate ligand, can limit the exocytotic process. Gamma-aminobutyric acid and serotonin demonstrate similar roles in reducing sympathetic nerve activity. In contrast to these inhibitory presynaptic mechanisms, facilitation of norepinephrine release appears to occur by way of neuronal angiotensin II receptor activation and perhaps through stimulation of sympathetic nerve membrane beta 2-receptors. An appreciation of these inhibitory and facilitator mechanisms is useful in the treatment of a variety of clinical conditions, including hypertension, heart failure, orthostatic hypotension, septic shock and a number of common withdrawal syndromes.
 ...
PMID:Modulation of peripheral sympathetic nerve transmission. 283 2

The contribution of neurohumoral factors to arterial pressure has been studied in several models of sodium-dependent hypertension including the deoxycorticosterone-saline, Dahl salt-sensitive rats, and reduced renal mass-saline. Observations from these animals have largely pointed to the sympathetic nervous system and arginine vasopressin (AVP) as the critical factors responsible for mediating the increased arterial pressure. Our work has indicated that the one-kidney, figure-8 renal wrap model of experimental hypertension is also sodium dependent. In these rats, prior sodium depletion prevented the development of hypertension whereas high sodium intake exacerbated the increase in arterial pressure. An activation of the sympathetic nervous system and increased AVP activity appeared to be responsible for the hypertension in rats maintained on normal and high sodium intake. Stimulation of the AVP and sympathetic nervous systems in sodium-dependent hypertension may be associated with a suppression of cardiovascular gamma-aminobutyric acid (GABA)-ergic function in the central nervous system. The inhibitory neurotransmitter, GABA, and an inhibitor of GABA uptake, nipecotic acid, lowered arterial pressure in a sodium-stimulated model of hypertension.
 ...
PMID:Neurohumoral mechanisms of sodium-dependent hypertension. 285 21

The present study examined the effect of lesion of cell bodies in the nucleus ambiguus area on the development of neurogenic hypertension and further explored the cardiovascular responses produced by chemical and electrical stimulation of the nucleus ambiguus and the neighboring C1 region. Three days after chemical lesion of the nucleus ambiguus with kainic acid, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of arterial pressure (157 +/- 7 vs 132 +/- 5 mm Hg) and heart rate (436 +/- 10 vs 374 +/- 10 beats/min) compared with those produced by sham lesion. Glutamate injected into the nucleus ambiguus increased arterial pressure and heart rate at 20 nmol/100 nl and decreased heart rate at 50 nmol/100 nl. Glutamate injected into the C1 area increased arterial pressure and heart rate at both doses. Gamma-Aminobutyric acid at 50 nmol/100 nl produced bradycardia and a fall in arterial pressure when injected into both the nucleus ambiguus and C1 area. The heart rate responses to gamma-aminobutyric acid and glutamate were attenuated in sinoaortic-deafferentated rats. The nucleus ambiguus and the C1 region were mapped using electrical stimulation with microelectrodes. All points stimulated in three anteroposterior sections in the nucleus ambiguus and the C1 area produced increases in arterial pressure, whereas bradycardia was restricted to the middle of three lateral coordinates associated with the center of the nucleus ambiguus and the C1 area ventral to the nucleus ambiguus.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1988 Jun
PMID:Role of the nucleus ambiguus in the regulation of heart rate and arterial pressure. 289 58

Microinjections of gamma-aminobutyric acid (GABA) and glycine, into the medial area of the nucleus tractus solitarii (NTS) of the rat, led to an increase in arterial pressure and heart rate. The GABA receptor antagonist bicuculline and the glycine receptor antagonist strychnine decreased both of these cardiovascular parameters whereas the GABA uptake inhibitor nipecotic acid produced hypertension. High K+ stimulation caused a calcium-dependent release of GABA and glycine from tissues in the area of the NTS. Our results suggest that GABA and glycine may modulate the cardiovascular control within the NTS.
 ...
PMID:Evidence for the presence of GABAergic and glycine-like systems responsible for cardiovascular control in the nucleus tractus solitarii of the rat. 303 55

In vivo extracellular recordings from rat supraoptic and paraventricular magnocellular neurosecretory cells (MNCs) indicate that putative vasopressin-secreting MNCs may be identified by an abrupt and brief cessation in firing consequent to a transient drug-induced rise in arterial pressure sufficient to activate arterial baroreceptors. In the diagonal band of Broca (DBB), a population of neurons projecting towards the supraoptic nucleus are activated during this drug-induced hypertension. Electrical stimulation in DBB selectively depresses supraoptic vasopressin-secreting MNCs. Intracellular recordings in perfused hypothalamic explants confirm a DBB-evoked bicuculline-sensitive and chloride-dependent postsynaptic inhibition, similar to that associated with the application of gamma-aminobutyric acid (GABA) in approximately half of supraoptic MNCs. Since bicuculline also selectively blocks baroreceptor-induced inhibition in supraoptic MNCs, it is proposed that the depressant baroreflex input to vasopressin-secreting MNCs involves a population of DBB neurons and GABAergic interneurons located close to MNCs. An excitatory and selective input to vasopressin-secreting MNCs follows chemoreceptor activation, possibly mediated by the A1 noradrenergic cell group in the ventrolateral medulla. Another excitatory input to both vasopressin- and oxytocin-secreting MNCs is triggered by circulating angiotensin II and appears to be relayed centrally through an angiotensinergic projection from the subfornical organ.
 ...
PMID:Cardiovascular input to hypothalamic neurosecretory neurons. 304 23

Recent studies have demonstrated that the neurons of the lower brainstem that are responsible for maintaining normal levels of arterial pressure reside in a specific area of the rostral ventrolateral medulla. In rat, the critical zone corresponds to a small region containing a subpopulation of the adrenergic C1 group, defined immunocytochemically by the presence of the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase. Neurons of this region (the C1 area), possibly including the adrenergic neurons, directly innervate preganglionic neurons in the spinal cord, and are tonically active and sympathoexcitatory. The excitatory transmitter released into the spinal cord is unknown. The discharge of C1 area neurons is locked to the cardiac cycle and, in turn, leads to firing of sympathetic preganglionic neurons. The C1 area neurons are inhibited by baroceptor input and mediate the vascular component of baroceptor reflexes. They also mediate somato-sympathetic pressor responses from skin and muscle and participate in reflex responses to hypoxia. The neurons are directly innervated by local neurons containing gamma-aminobutyric acid, acetylcholine, enkephalin, and substance P, all of which modulate arterial pressure. The C1 area is the site of the hypotensive actions of clonidine. Clonidine appears to act on imidazole receptors in the C1 area to lower arterial pressure. The natural ligand for these receptors may be a newly defined substance in brain, clonidine-displacing substance. Neurons of the C1 area appear to be the critical neuronal group governing the normal resting and reflex control of arterial pressure. They may play a critical role in the maintenance of elevated arterial pressure in hypertension and as a site of action of antihypertensive drugs.
Hypertension 1988 Feb
PMID:The C1 area of the brainstem in tonic and reflex control of blood pressure. State of the art lecture. 327 78

Effects of oral treatment with taurine on fluid intakes produced by renin were assessed in spontaneously hypertensive rats of the Okamoto strain (SHR). Renin injected into the preoptic area increased water intake and evoked salt (2.7% NaCl solution) intake, and angiotensin II injected into this area increased water intake, but not salt intake, in both SHR and control normotensive Wistar-Kyoto rats (WKY). The salt intake elicited by renin, but not water intake produced by renin or angiotensin II, was potentiated in SHR. These effects of renin and angiotensin II on fluid intakes were antagonized by previous administration of taurine or gamma-aminobutyric acid into the cerebral ventricles in both strains. When SHR received water containing 3% taurine from 32 to 105 days of age, development of hypertension was inhibited. Renin administered into the preoptic area at 105 days of age caused an increase in salt intake, but the increase was markedly inhibited by the oral administration of taurine as well. These results show that salt appetite produced by centrally administered renin is exaggerated in SHR and that development of hypertension as well as renin-induced salt appetite in SHR is inhibited by dietary taurine.
Hypertension 1987 Oct
PMID:Inhibition of hypertension and salt intake by oral taurine treatment in hypertensive rats. 330

Pyridoxal phosphate is the coenzyme of various decarboxylases involved in the formation of monoamine neurotransmitters such as gamma-aminobutyric acid, serotonin, dopamine, and norepinephrine. Adult male Sprague-Dawley rats placed on a pyridoxine-deficient diet for 8 weeks showed significant hypertension compared with pyridoxine-supplemented controls. Hypothalamic contents of pyridoxal phosphate, gamma-aminobutyric acid, and serotonin in the pyridoxine-deficient rats were significantly lower than those in pyridoxine-supplemented controls. Hypertension was associated with sympathetic stimulation. Treatment of pyridoxine-deficient rats with a single dose of pyridoxine (10 mg/kg body weight) reversed the blood pressure to normal levels within 24 hours, with concomitant restorations of hypothalamic serotonin and gamma-aminobutyric acid as well as the return of plasma norepinephrine and epinephrine to normal levels. Also, pyridoxine treatment reversed the hypothalamic hypothyroidism observed in pyridoxine-deficient rats. These results indicate an association between pyridoxine deficiency and sympathetic stimulation leading to hypertension.
Hypertension 1988 Apr
PMID:Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat. 335 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>