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

Prolonged stimulation of tissues by adrenergic agonists may lead to diminished responsiveness of the tissues to subsequent activation by catecholamines; this phenomenon has been termed desensitization or tachyphylaxis. We have examined the in vivo consequences of prolonged stimulation of vascular alpha-adrenergic receptors in rats harboring pheochromocytoma, a tumor that secretes catecholamines. In both early (3-4 weeks after implantation) and late (6-7 weeks after implantation) stages of tumor development, New England Deaconess Hospital rats with transplanted pheochromocytomas developed hypertension and tachycardia and had plasma dopamine and norepinephrine concentrations markedly greater than controls. In both these stages of pheochromocytoma, pressor responses to several vasoconstrictors were examined after pithing. Rats with the tumor were found to become progressively subsensitive to alpha-adrenergic agonists. In the early phase of pheochromocytoma, loss in sensitivity was found for both alpha 1- and alpha 2-adrenergic agonists, whereas responsiveness to the nonadrenergic vasoconstrictors Arg-vasopressin and angiotensin-II was intact (homologous desensitization). However, in the later stage of pheochromocytoma, pressor responses to all these vasoconstrictive agents and also to stimulation of the complex sympathetic outflow were found to be subsensitive (heterologous desensitization). In plasma membranes prepared from mesenteric arteries of early stage tumor-bearing rats, [3H]prazosin binding sites were significantly decreased to 150 +/- 12 fmol/mg vs. 234 +/- 19 fmol/mg in controls. [3H]Yohimbine binding sites were not significantly altered. Our results show that both postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses can be specifically attenuated in the presence of chronically elevated endogenous catecholamine levels produced by pheochromocytoma and that each alpha-receptor subtype may be differently regulated in the development of desensitization.
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PMID:Desensitization of postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses in rat harboring pheochromocytoma. 303 68

Adult wolves (Canis lupus) were immobilized with 6.6 mg/kg ketamine hydrochloride (KET) and 2.2 mg/kg xylazine hydrochloride (XYL) administered intramuscularly. Induction time was 4.6 +/- 0.3 min (mean +/- SE). Immobilization resulted in significant bradycardia and hypertension (P less than 0.05). Twenty min after induction, the wolves were given 0.05-0.60 mg/kg yohimbine hydrochloride (YOH). Yohimbine given intravenously produced dose-related increases in heart rate (HR) with doses greater than 0.15 mg/kg resulting in extreme tachycardia (greater than 300 bpm). All doses of YOH caused a temporary decrease in mean arterial blood pressure (MABP) with some individual animals manifesting profound hypotension (less than 30 torr) at doses greater than 0.15 mg/kg. Increasing the dose of YOH above 0.15 mg/kg did not significantly decrease either arousal or ambulation times. Administering YOH at 40 or 60 min after induction resulted in decreased arousal and ambulation times. Stimulation by weighing and taking repeated blood samples during anesthesia did not shorten arousal times. We recommend that wolves immobilized with XYL-KET be antagonized with doses of YOH less than 0.15 mg/kg.
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PMID:Cardiovascular and behavioral responses of gray wolves to ketamine-xylazine immobilization and antagonism by yohimbine. 362 8

The centrally mediated cardiovascular changes induced by clonidine were studied in conscious rats. Clonidine administered intracerebroventricularly (i.c.v.), and intravenously (i.v.) caused hypotension following an initial pressor response. I.v. clonidine caused significant greater hypotension than i.c.v. clonidine (30 micrograms/kg; p less than 0.05). With the 30 micrograms/kg i.c.v. dose, a tachycardia was observed in all rats following initial transient bradycardia. No tachycardia was observed when clonidine was administered i.v. Propranolol (3 mg/kg i.v.) did not modify the cardiovascular actions of i.c.v. clonidine except initial pressure response. While combined treatment with propranolol (3 mg/kg i.v.) and atropine (1 mg/kg i.v.) abolished both the bradycardic and tachycardic actions of i.c.v. clonidine (30 micrograms/kg), but did not modulate the hypotensive action. Yohimbine (30 micrograms/kg i.c.v.) converted the hypotension induced by i.c.v. clonidine (30 micrograms/kg) to hypertension, attenuated the bradycardia but did not modulate the tachycardia. The same dose of i.c.v. yohimbine attenuated the hypotensive effect of i.v. clonidine (30 micrograms/kg) but did not affect the initial pressor response. Prazosin (30 micrograms/kg i.c.v.) did not modulate either phase of the heart rate response to i.c.v. clonidine. These results provide evidence of centrally mediated pressor and tachycardic actions of clonidine in conscious rats. The tachycardia appears to be mediated through the inhibition of parasympathetic tone and is not dependent on alpha-adrenoceptor mechanism. In conscious rats the opposing influence of centrally mediated pressor and depressor actions may result in the apparently low hypotensive potency of i.c.v. clonidine.
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PMID:Tachycardic and hypertensive effects of centrally administered clonidine in conscious rats. 372 2

Many studies have suggested that alpha-adrenergic receptors on vascular smooth muscle are heterogeneous and that both alpha 1- and alpha 2-adrenergic receptors can cause vasoconstriction when stimulated. We explored this hypothesis in normal humans by comparing the capacity of yohimbine, an alpha 2-adrenergic receptor antagonist, and prazosin, an alpha 1-adrenergic receptor agonist, with differentially blocked pressor responses to phenylephrine, an alpha 1-adrenergic receptor agonist, and epinephrine, a nonselective alpha-agonist. We studied these responses in normal male volunteers who had been pretreated with propranolol (80 mg orally every 8 hours for 5 days) to obviate stimulation of beta-receptors by either agonist. We found differential effects of the antagonists on responses to the two agonists. Yohimbine induced a 3.1-fold (+/- 0.5) shift in the dose of epinephrine, which raised blood pressure 25 mm Hg, and only a 1.9-fold (+/- 0.2) shift in the response to phenylephrine (p less than 0.01). Prazosin induced a 2.4-fold (+/- 0.5) shift in the responses to epinephrine and a 4.5-fold (+/- 1.2) shift in the response to phenylephrine (p less than 0.05). These data are consistent with the notion that alpha-adrenergic receptors in the human vasculature are not homogeneous, but rather may be subdivided into at least two subtypes, one resembling alpha 1-adrenergic receptors and the other resembling alpha 2-adrenergic receptors.
Hypertension
PMID:Evidence for the existence of vascular alpha 2-adrenergic receptors in humans. 608 19

Blood pressure and heart rate were recorded in the sea gull, Larus argentatus, under light pentibarbitone anaesthesia. Clonidine 10(-7) and 10(-8) mol . kg-1 (27 and 2.7 microgram . kg-1) i.v. produced a biphasic effect on blood pressure, a brief initial increase being followed by a prolonged hypotensive response. There was an immediate reduction in heart rate rate which persisted throughout the hypotensive phase. After spinal transection at the level of C4, clonidine administration elicited hypertension and bradycardia. Bilateral vagotomy abolished the effect of clonidine on heart rate but did not alter the blood pressure response. Vagotomy in combination with spinal transection abolished the effect of clonidine on heart rate but the hypertensive response was accentuated. Yohimbine 10(-7) or 10(-6) mol . kg-1 (0.039 or 0.39 mg . kg-1) given 5 min after clonidine 10(-7) mol.kg-1 (27 microgram . kg-1) effectively antagonized the cardiovascular effects of clonidine, while prazosin 10(-7) or 10(-6) mol . kg (0.042 or 0.42 mg . kg-1) had no such effect. We conclude that clonidine acts in the central nervous system of the sea gull to produce a lowering of blood pressure and heart rate. These effects are mediated by central inhibition of sympathetic activity and, in the case of the heart rate, mostly by central activation of vagal activity to the heart. This central action of clonidine involves activation of alpha-adrenoceptors which are blocked by yohimbine but not by prazosin and therefore may belong to the alpha 2 subtype.
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PMID:Cardiovascular effects of clonidine in an avian species, Larus argentatus. 612 Apr 70

In this review, we examine the changes in sexual function that accompany deviations from "normal" physiological states. We propose that the changes one observes in many altered physiological states should not be viewed in isolation. We describe our paradigms for assessing sexual function, and proceed to evaluate how sexual function changes with hormonal deprivation and aging, in rat models for hypertension, in severe hyperprolactinemia, in streptozotocin-induced diabetes, after chronic alcohol intake, after chronic morphine administration, and after exposure to the heavy metal, cadmium. We will provide evidence for the involvement of adrenergic transmitters and two neuropeptides, neuropeptide Y and somatostatin, in the neuroendocrine regulation of sexual behavior. Finally, we compare and contrast the changes observed relative to the changes seen in "normal" aging in rats. The sequence of age-related changes in sexual function is distinct. The first change observed is a decrement in ex copula erectile reflexes. Next are decreases in ejaculatory threshold, followed shortly by increases in initiation and reinitiation of copulation after ejaculation. This is followed by a decrement in the number of males copulating to ejaculation. Finally, there is a failure to initiate the copulatory process. This sequelae is relatively common, being evident after castration, with hyperprolactinemia, and after exposure to cadmium. The data available for sexual function in hypertension is incomplete and modified by the etiology, but a suggestion for this sequelae is seen in SHR. In contrast, sexual dysfunction associated with chronic morphine administration appears to be due to an initial deficit in motivational aspects. Testosterone reverses sexual dysfunction associated with castration, but not with idiopathic sexual inactivity, nor with sexual dysfunction associated with aging, diabetes, or chronic morphine administration. Comparing sexual function in rat models for hypertension, diabetes and chronic ethanol leads to the conclusion that increases in blood pressure, like decreases in testosterone, cannot be the primary causal factor for sexual dysfunction. Age, hormonal history of the subject, and the age at castration influence changes in sexual function. Age-related sexual dysfunction appears to be contributed to by changes in adrenergic-neuropeptidergic, to include sympathetic, systems. Site-specific administration of NPY induces alterations in parameters of copulatory behavior which mimic those seen in aging and the retention of ejaculatory behavior with aging is associated with site-selective attenuation (or reversal) of age-associated changes in NPY content. Yohimbine enhances copulatory activity in castrated and aging rats, and attenuates or reverses the antisexual effects of clonidine, epinephrine and somatostatin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sexual function in altered physiological states: comparison of effects of hypertension, diabetes, hyperprolactinemia, and others to "normal" aging in male rats. 763 May 83

The purpose of this study has been to test the hypothesis of an alpha 2-adrenoreceptor alteration in human essential hypertension. The design of the study involved the oral administration of 10 mg yohimbine, an alpha 2-adrenergic antagonist, to 25 healthy volunteers and 29 sex- and age-matched untreated hypertensive patients. Volunteers and patients were studied twice in random order, after placebo or yohimbine treatment, in supine and upright positions. Arterial pressure and heart rate were monitored by servoplethysmomanometry, and venous plasma catecholamines were determined by HPLC with electrochemical detection. Yohimbine induced a significant increase in diastolic pressure only in the hypertensive patients. Plasma norepinephrine was increased significantly in both yohimbine-treated groups, but the percent increase of plasma norepinephrine after the standing test was decreased significantly only in the healthy yohimbine-treated subjects. Plasma dopamine was increased significantly only in the healthy yohimbine-treated subjects. The response of plasma dopamine to the upright position was modified only in the healthy yohimbine-treated subjects. The decrease observed after 2 min of standing was abolished, showing the involvement of alpha 2-adrenoreceptors in the physiologic response of plasma catecholamines in healthy volunteers. Our data may be consistent with some in vivo evidence of an alpha 2-adrenoreceptor desensitization or an alteration in the balance of alpha-adrenoreceptors in human hypertension.
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PMID:Yohimbine effects on blood pressure and plasma catecholamines in human hypertension. 766 40

The present investigation was undertaken to see whether a long-term inhibition of adenosine receptors--leading to hypertension--interferes with alpha 2-adrenoceptor-mediated modulation of noradrenaline release. Rat tail arteries were removed from normal and from hypertensive animals obtained by chronic treatment with intraperitoneally infused DPSPX (1,3-dipropyl-8-sulphophenylxanthine) or orally administered L-NAME (NG-Nitro-L-arginine methyl ester). To study prejunctional effects, the influence of UK-14,304 (5-bromo-6(imidazoline-2-ylamino)-quinoxaline) and yohimbine on the overflow of tritium evoked by electrical stimulation (100 V; 1 Hz; 2 ms; 5 min) from tissues preloaded with 3H-noradrenaline was analysed. To study postjunctional effects, concentration-response curves to UK-14,304 were determined. In DPSPX-treated rats there was an enhancement of the prejunctional effects of UK-14,304: its Ec30% was reduced from 381 (250; 579) to 85 (73; 99) nmol.l-1 (n = 5; P < 0.05) and its maximal effect--expressed as percent reduction of tritium overflow-increased from 45 +/- 5% to 61 +/- 5% (n = 6; P < 0.05). In L-NAME-treated rats there was no change in either of these two parameters. At the postjunctional level, there was no change in the sensitivity to UK-14,304 in tissues from either DPSPX- or L-NAME-treated rats. Yohimbine (10-1000 nmol.l-1) caused a concentration-dependent increase of tritium overflow evoked by electrical stimulation in both control and hypertensive animals (either DPSPX- or L-NAME-treated).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term administration of 1,3-dipropyl-8-sulphophenylxanthine (DPSPX) alters alpha 2-adrenoceptor-mediated effects at the pre- but not at the postjunctional level. 770 27

Recent studies indicate that norepinephrine-induced contractile oscillations in the tail artery from stroke-prone spontaneously hypertensive rats (SHRSP) may be a vascular phenomenon independent of blood pressure level. The objectives of this study were: (1) to characterize pharmacologically the alpha-adrenoceptor mediating norepinephrine-induced oscillations in tail artery; and (2) to investigate the relationship between blood pressure level, altered by treatments with hydralazine/hydrochlorothiazide or the angiotensin converting enzyme inhibitor ramipril, and the observation of norepinephrine-induced oscillations in tail artery. The alpha 2-adrenoceptor agonists clonidine and guanabenz potently stimulated oscillatory contractions in the tail artery while the alpha 1-adrenoceptor agonists phenylephrine and methoxamine were considerably less potent. Yohimbine, an alpha 2-adrenoceptor antagonist, but not the alpha 1-adrenoceptor antagonist prazosin demonstrated high affinity for the receptor mediating norepinephrine-induced oscillatory contractions. These results support the hypothesis that norepinephrine-induced oscillatory contractions in the tail artery from SHRSP occur primarily through stimulation of alpha 2-adrenoceptors. Ramipril lowered blood pressure in SHRSP after 4 weeks of treatment during 6-10 weeks of life but did not alter the ability of the alpha 2-adrenoceptor agonist clonidine (10(-5) M) to induce contractile oscillations in tail arteries from SHRSP, indicating these oscillations are not a secondary effect of high blood pressure. These studies suggest that norepinephrine-induced oscillations in tail artery from SHRSP may be a vascular trait separate and distinct from blood pressure level and angiotensin II expression early in life.
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PMID:Effect of ramipril on alpha-adrenoceptor-mediated oscillatory contractions in tail artery of hypertensive rats. 828 89

Yohimbine is an alpha 2 adrenoreceptor antagonist occasionally used in the treatment of impotence. Overdose of this drug is uncommon. We describe a 62-year-old male who ingested 100, 2.0 mg tablets whose only adverse effects were tachycardia, hypertension, and anxiety of brief duration. The limited experience to date suggests a benign course even after massive overdose. Observation would seem to be the management of choice.
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PMID:Benign course after massive ingestion of yohimbine. 834 May 84


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