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)

Juvenile spontaneously hypertensive rats (SHR) have higher plasma levels of catechols and markedly larger catechol responses to yohimbine than do normotensive Wistar-Kyoto rats, indicating increased sympathoadrenal outflow and increased alpha 2-adrenergic receptor-mediated restraint of peripheral catecholamine release during hypertension development in SHR. Yohimbine-induced catecholamine release and metabolism in the posterolateral hypothalamus of the brain were assessed in juvenile (6 to 7 weeks) and adult (15 to 16 weeks) SHR and Wistar-Kyoto rats. In vivo microdialysis was used to obtain samples for measurements of norepinephrine, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid in conscious animals before and after yohimbine injection (1 mg/kg IV) beginning 24 hours after probe implantation. Catecholamine synthesis was examined from elevations of 3,4-dihydroxyphenylalanine levels after probe perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. In adults, SHR had higher dialysate norepinephrine (277 +/- 38 versus 181 +/- 35 pg/mL), dihydroxyphenylglycol (3260 +/- 509 versus 2231 +/- 201 pg/mL), methoxyhydroxyphenylglycol (2659 +/- 369 versus 1890 +/- 144 pg/mL), and dihydroxyphenylacetic acid (46,312 +/- 5512 versus 13,187 +/- 1963 pg/mL) levels and markedly larger increases in 3,4-dihydroxyphenylalanine levels after NSD-1015 than Wistar-Kyoto rats. In juveniles, SHR had larger proportionate increments in microdialysate norepinephrine levels after yohimbine than Wistar-Kyoto rats (85% versus 25%). Although juvenile SHR and Wistar-Kyoto rats had similar NSD-1015-elicited increments in 3,4-dihydroxyphenylalanine levels, systemic yohimbine enhanced the NSD-1015-elicited 3,4-dihydroxyphenylalanine elevations in juvenile SHR but not in Wistar-Kyoto rats. These findings suggest augmented norepinephrine release and catecholamine synthesis in the posterolateral hypothalamus of adult SHR and augmented alpha 2-adrenergic receptor restraint of both norepinephrine release and catecholamine synthesis in juvenile SHR.
Hypertension 1993 Oct
PMID:In vivo hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats. 840 51

We have studied the sympathetic response to blockade of presynaptic alpha 2-adrenoceptors in essential hypertension by measuring plasma concentrations of noradrenaline after a single oral dose of yohimbine, an alpha 2-adrenoceptor antagonist. Mean baseline plasma noradrenaline and adrenaline concentrations were similar in the hypertensive and normotensive groups. Yohimbine (0.2 mg x kg-1 orally) caused a lesser increase in the plasma concentrations of noradrenaline in hypertensive patients (+67%) than in normotensive subjects (+178%) and a pressor response in hypertensive (but not in normotensive) patients. These results are consistent with an alteration in the balance of alpha-adrenoceptors (for example presynaptic alpha 2-adrenoceptor desensitization and post-synaptic alpha 1-adrenoceptor hyper-responsiveness) which would help to develop and/or maintain arterial hypertension.
 ...
PMID:The effect of yohimbine on sympathetic responsiveness in essential hypertension. 845 67

1. The recovery of the clonidine-induced hypotension, bradycardia and sympatho-inhibition produced by several putative alpha 2-adrenoceptor antagonists was investigated in pentobarbitone anaesthetized rats. The activity of four substances containing an imidazoline structure: idazoxan, methoxy-idazoxan, BRL44408 and atipamezole was compared with the effect of fluparoxan, yohimbine and L-657,743; in addition the effect of the alpha 1-adrenoceptor antagonist, prazosin, was also studied. 2. Prazosin (0.03-1 mg kg-1, i.v.) failed to alter the sympatho-inhibitory and hypotensive effects of clonidine (10 micrograms kg-1, i.v.). L-657,743 (0.01-1 mg kg-1, i.v.) induced a recovery of blood pressure, heart rate and renal sympathetic nerve activity. Yohimbine (0.03-3 mg kg-1, i.v.) completely reversed the sympatho-inhibitory effect of clonidine but did not alter its hypotensive effect. 3. The four imidazoline drugs: idazoxan (10-300 micrograms kg-1, i.v.), methoxy-idazoxan (1-100 micrograms kg-1, i.v.), BRL44408 (0.1-3 mg kg-1, i.v.) and atipamezole (0.03-1 mg kg-1, i.v.) and fluparoxan (10-300 micrograms kg-1, i.v.) reversed the clonidine-induced hypotension but produced only a partial recovery of the renal sympathetic nerve activity and of the heart rate. After pretreatment with prazosin (0.1 mg kg-1, i.v.), the recovery of the sympathetic nerve activity elicited by these compounds was significantly higher. In hexamethonium (10 mg kg-1, i.v.) pretreated rats, these five drugs induced dose-related hypertension which was reduced by pretreatment with prazosin (0.1 mg kg-1, i.v.). 4. Our results indicate that the putative alpha 2-adrenoceptor antagonists idazoxan, methoxy-idazoxan, BRL44408, atipamezole and fluparoxan also have a peripheral hypertensive effect which is mediated through activation of vascular alpha 1-adrenoceptors; this property of the compounds may be partly responsible for the reversal of the hypotensive action of clonidine. Considering the structure and the affinities of the drugs tested, our data indirectly suggest that alpha 2A-adrenoceptors may be implicated in the central sympatho-inhibitory effects of clonidine.
 ...
PMID:A comparative study of the reversal by different alpha 2-adrenoceptor antagonists of the central sympatho-inhibitory effect of clonidine. 882 53

Increased vascular resistance during systemic nitric oxide synthase (NOS) inhibition is dependent on adrenergic vasoconstriction. This study tested the hypothesis that increased vascular sensitivity to adrenergic agonists contributes to this vasoconstriction. Superior mesenteric arteries and thoracic aortae from male Sprague-Dawley rats drinking water containing N omega-nitro-L-arginine (L-NNA; 14 days, 60 mg.kg-1.day-1) and control rats were-cut into helical strips, and endothelium was removed for contractile experiments. L-NNA arteries were more sensitive to UK-14304 (alpha 2-adrenergic agonist) and norepinephrine (NE), whereas responses to phenylephrine (PE) were not different concentration causing 50% maximal response (EC50), L-NNA vs. control: UK-14304, 0.071 vs. 0.71 mumol/l; NE, 1.15 vs. 9.95 nmol/l]. Yohimbine, an alpha 2-selective antagonist, caused a concentration-dependent inhibition of contraction to NE only in L-NNA arteries (EC50 = 6.3 vs. 1.6 nmol/l at 1 nmol/l yohimbine), whereas prazosin shifted NE curves similarly in arteries from both groups. Yohimbine (10 nmol/l) inhibited contractions to UK-14304 (EC50 = 59 mumol/l vs. 17 mumol/l) but not contractions to PE, whereas prazosin inhibited both. These data indicate that L-NNA-induced hypertension leads to increased sensitivity of prazosin-sensitive alpha 2-adrenoceptors, an upregulation that could cause the increased vasoconstrictor response to NE in this model of hypertension.
 ...
PMID:Increased vascular responsiveness to alpha 2-adrenergic stimulation during NOS inhibition-induced hypertension. 943 12

Quality and number of subjects in blinded controlled clinical trials about the nutrition and dietary supplements discussed here is variable. Glucosamine sulfate and chondroitin sulfate have sufficient controlled trials to warrant their use in osteoarthritis, having less side effects than currently used nonsteroidal anti-inflammatory drugs, and are the only treatment shown to prevent progression of the disease. Dietary supplements of ephedrine plus caffeine for weight loss (weight loss being the current first line recommendation of physicians for osteoporosis) show some promise, but are not sufficient in number of study subjects. Phenylpropanolamine is proven successful in weight loss. Both ephedrine and phenylpropanolamine have resulted in deaths and hence are worrisome [table: see text] as an over-the-counter dietary supplement. Other commonly used weight loss supplements like Cola acuminata, dwarf elder, Yohimbine, and Garcinia camborgia are either lacking controlled clinical trials, or in the case of the last two supplements, have clinical trials showing lack of effectiveness (although Garcinia has been successful in trials as part of a mixture with other substances, it is unclear if it was a necessary part of the mixture). Safety of these weight loss supplements is unknown. Chromium as a body building supplement for athletes appears to have no efficacy. Creatine may help more in weight lifting than sprinting, but insufficient study subjects and safety information make more studies necessary. Carbohydrate loading is used commonly before endurance competitions, but may be underused as it may be beneficial for other sport performances. Supplements for muscle injury or cramps have had too few studies to determine efficacy. Although proper rehydration with fluids and electrolytes is necessary, a paucity of actual studies to maximize prophylactic treatment for exercise induced cramping still exists. Nutritional supplements for cardiovascular disorders are generally geared to prevention. The United States Department of Agriculture has good recommendations to prevent atherosclerosis; a stricter version by Ornish was shown to reverse coronary heart disease, and the low meat, high fruit, and vegetable DASH diet has been found to decrease hypertension. The epidemiologic studies of hyperhomocysteinemia are impressive enough to give folic acid (or vitamin B6 or B12) supplements to those with elevated homocysteine levels and test patients who have a history of atherosclerotic disease, but no controlled clinical trials have been completed. Soluble fiber has several positive studies in reduction of cholesterol levels and generally is accepted. The data on vitamin E are the most confusing. This vitamin was not helpful in cerebrovascular prevention in China and not helpful at relatively small doses (50 mg) in the United States or Finland against major coronary events. Levels of 400 mg appeared to decrease cardiovascular disease in the United States in studies based on reports by patients and in one large clinical trial. Vitamin E also was successful in prevention of restenosis after PTCA in one clinical trial. Both of these clinical trials need to be repeated in other developed country populations. Some nutritional and dietary supplements are justifiably useful at this point in time. Several meet the criteria of a late Phase 3 FDA clinical trial (where it would be released for public use), but many dietary supplements have insufficient numbers of studies. Some deaths also have occurred with some supplements. If these supplements were required to undergo clinical trials necessary for a new drug by the FDA, they would not be released yet to the public. Several nontoxic supplements appear promising, though need further study. Because they have essentially no toxicity (such as folic acid with B12, soluble fiber, and vitamin E) and may have efficacy, some of these supplementations may be useful now, without randomized clinical trials.
 ...
PMID:Nutrition and dietary supplements. 1051 85

Administration (3 to 100 microg/kg IV) of clonidine, rilmenidine, and an imidazoline derivative, 2-(2-chlorophenylamino)imidazoline, in pithed nonstimulated rabbits caused a dose-dependent increase in mean arterial pressure without affecting heart rate. Prazosin (0.1 mg/kg IV) almost abolished the pressor responses to 2-(2-chlorophenylamino)imidazoline, partially inhibited those induced by clonidine, but failed to affect those elicited by rilmenidine. In contrast, yohimbine (1 mg/kg IV) blunted the pressor responses of the 3 drugs. In sympathetically stimulated pithed rabbits, 2-(2-chlorophenylamino)imidazoline induced only pressor effects, whereas clonidine and rilmenidine caused a transient pressure increase followed by a dose-dependent depressor effect. Yohimbine abolished the depressor effect of both drugs, which may have involved presynaptic alpha(2)-adrenoceptors. In conclusion, peripheral effects of 2-(2-chlorophenylamino)imidazoline and clonidine involved at least alpha(1)- and alpha(2)-adrenoceptor activation, whereas pressor and depressor effects of rilmenidine were mediated by alpha(2)-adrenoceptors.
Hypertension 1999 Oct
PMID:Cardiovascular effects of clonidine-like drugs in pithed rabbits. 1052

BACKGROUND: Restraint-stress and administration of drugs that precipitate hypertension induce heat-shock protein (HSP) expression in the aorta. The exact mechanism supporting this hypertension-related HSP response is unclear because HSP induction is blocked by receptor-selective and nonselective antihypertensive agents. METHODS AND RESULTS: To identify mechanisms contributing to the pharmacological/physiological regulation of the HSP response in cardiovascular tissues, we administered clonidine to awake and freely moving animals to determine its effect on HSP expression in vivo. Inconsistent with previous work, we found that clonidine produced a dose-dependent and transient increase in HSP70 mRNA levels in the aorta. No other tissue examined displayed an HSP response after clonidine administration. Clonidine-induced HSP expression was not restricted to the HSP70 family; HSP89alpha, HSP89beta, and HSP60 were also induced. Interestingly, no heat-shock element-binding activity was observed after clonidine administration, suggesting that unusual transcriptional regulatory mechanisms mediate this response. Yohimbine and nifedipine blocked HSP70 mRNA expression, whereas isoproterenol, mecamylamine, and reserpine had no effect. CONCLUSIONS: The functional consequence of HSP expression in cardiovascular tissues may be to alter the responsiveness of cells in these tissues to subsequent drug or stress exposures, thereby implicating the HSP response as an important component of cardiovascular homeostasis. If so, treatment of mammalian organisms with drugs capable of inducting selective HSP expression in vascular tissue may alter the progression of cardiovascular disease processes.
 ...
PMID:Clonidine-Induced Heat-Shock Protein Expression in Rat Aorta. 1068 95

Behavioral stress is likely to contribute to the development of hypertension in susceptible individuals. We reported that hemodynamic response patterns to acute startle vary and that those patterns predict the predisposition of rats to sustained stress-induced elevations in arterial pressure. Since considerable evidence suggests that central catecholamines and corticotropin releasing factor (CRF) contribute to the regulation of arterial pressure and the development of hypertension, we investigated the role of central alpha-adrenergic receptors and CRF in mediating different hemodynamic response patterns to acute cold water stress in conscious rats. Rats were instrumented for arterial pressure, heart rate and cardiac output determination and for intracerebroventricular (icv) administration of selective antagonists. After acclimation to a water tight cage, ice water (1 cm deep) was rapidly added then drained 1 min later. Although the early startle response to cold water stress elicited a pressor response in all rats, the hemodynamic response pattern varied between rats. Vascular responders (n=19) had an initial considerable increase in systemic vascular resistance and a decrease in cardiac output. In contrast, mixed responders (n=11) had a smaller increase in vascular resistance and an increase in cardiac output. Pretreatment with phentolamine (30 microgram/5 microliter, icv, n=8), prazosin (10 microgram/5 microliter, icv, n=12) or alpha-helical CRF(9-41) (10 microgram/5 microliter, icv, n=9) prevented the decrease in cardiac output elicited by acute cold water stress in vascular responders without affecting mixed responders. Yohimbine (3 microgram/5 microliter, icv, n=8) pretreatment did not alter hemodynamic responses. Therefore, we conclude that central alpha(1)-adrenoceptors and CRF mediate the specific hemodynamic response patterns to acute startle and may be responsible for the predisposition to develop hypertension in vascular responders.
 ...
PMID:Central alpha-adrenergic receptors and corticotropin releasing factor mediate hemodynamic responses to acute cold stress. 1264 70

Alpha-2 adrenoreceptor stimulation profoundly augments baroreflex-mediated bradycardia presumably through parasympathetic activation. We tested the hypothesis that endogenous alpha-2 adrenergic tone mediates a similar response. In 10 healthy men (age: 33+/-3 years; body mass index: 24+/-1.3 kg/m(2)), we determined baroreflex control of heart rate and sympathetic traffic after ingestion of the selective alpha-2 adrenoceptor antagonist yohimbine (20 mg) or placebo. Testing was conducted in a randomized, double-blind, crossover fashion. We measured heart rate, brachial and finger blood pressure, and muscle sympathetic nerve activity. Sympathetic and parasympathetic baroreflex curves were determined using incremental phenylephrine and nitroprusside infusions (0.3, 0.6, 0.9, 1.2, and 1.5 microg/kg per minute). Plasma norepinephrine increased with yohimbine (50+/-38 ng/L; P<0.05) and was unchanged with placebo (2.2+/-7.6 ng/L). Blood pressure increased 13+/-4/8+/-1 mm Hg with yohimbine and 6+/-2/3+/-1 mm Hg with placebo (P<0.01). HR increased 5+/-1 bpm with yohimbine but did not change with placebo (P<0.01). Ninety minutes after drug ingestion, resting muscle sympathetic nerve activity was similar with yohimbine and with placebo. Baroreflex control of heart rate was decreased with yohimbine (6 ms/mm Hg versus 10 ms/mm Hg; P<0.01) and reset to higher blood pressure and heart rate values. In contrast, yohimbine did not alter the sympathetic baroreflex curve. Yohimbine selectively attenuates baroreflex heart rate control in normotensive young men possibly through parasympathetic mechanisms.
Hypertension 2007 Nov
PMID:Yohimbine attenuates baroreflex-mediated bradycardia in humans. 1787 19

We studied hypertension-associated changes in prejunctional alpha(2) adrenergic receptor (alpha(2)-AR) function using amperometry to monitor in vitro norepinephrine (NE) measured as oxidation currents. Vasoconstriction was measured using video imaging. NE release was induced by electrical stimulation of sympathetic nerves associated with mesenteric arteries (MA) and veins (MV) of sham and DOCA-salt hypertensive rats. NE oxidation currents were larger in DOCA-salt compared to sham MA; there were no differences between currents in sham and DOCA-salt MV. Increases in NE oxidation currents followed a multi-exponential time course in sham MA. In DOCA-salt MA and sham and DOCA-salt MV, the time course was mono-exponential. Yohimbine (alpha(2)-AR antagonist, 1 microM), caused a mono-exponential increase in NE oxidation currents in sham and DOCA-salt MA. Yohimbine increased NE oxidation currents and constrictions more in sham compared to DOCA-salt MA and compared to MV. UK 14,304 (alpha(2)-AR agonist, 1.0 microM), reduced currents less in DOCA-salt MA and sham and DOCA-salt MV compared to sham MA. Prazosin (alpha(1)-AR antagonist, 0.1 microM) did not alter NE oxidation currents. Prazosin inhibited constrictions more in DOCA-salt compared to sham MA and almost completely blocked constrictions in sham and DOCA-salt MV. Prazosin-resistant constrictions in MA were blocked by the P2 receptor antagonist, PPADS (10 microM). Prejunctional alpha(2)-ARs modify NE concentrations near neuroeffector junctions in MA and MV. alpha(2)-AR function is most prominent in MA and is impaired in DOCA-salt MA but not MV. Purinergic transmission predominates in sham MA. NE is the dominant vasoconstrictor in DOCA-salt MA and sham and DOCA-salt MV.
 ...
PMID:Alterations in sympathetic neuroeffector transmission to mesenteric arteries but not veins in DOCA-salt hypertension. 1991 50


<< Previous 1 2 3 4 5 Next >>