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

The prevalence of hypertension increases with age. Multiple physiologic factors are involved in the development of hypertension in the elderly. Alpha1-adrenergic blocking agents lower blood pressure through a reduction in total peripheral resistance. Prazosin, terazosin, and doxazosin have been shown to be equally effective in reducing blood pressure in older persons. The bioavailability, terminal elimination half-life, and volume of distribution of prazosin is increased in the elderly. Hybrid drugs, such as ketanserin, urapidil, and indoramin are also effective in lowering blood pressure. Ketanserin seems to have a greater effect on blood pressure reduction in persons older than 60 years of age. Alpha1-adrenergic blockers may be used safely in patients with diabetes, asthma, and hyperlipidemia.
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PMID:Antihypertensive therapy in the geriatric patient: II. A review of the alpha1-adrenergic blocking agents. 809 84

The vasoconstrictor responses to alpha-1 adrenoceptor agonists, binding behavior of alpha-1 adrenoceptors and postreceptor events in the mesenteric vasculature from deoxycorticosterone acetate-salt hypertensive rats were studied. The reactivity of perfused mesenteric artery to norepinephrine (NE) and phenylephrine, but not KCl, was enhanced significantly in the hypertensive rats compared with control rats. Prazosin antagonized the pressor response to NE more effectively in the hypertension than in the control. [3H]Prazosin binding was saturable and a single class of specific sites. Scatchard analysis revealed that the dissociation constant for [3H]prazosin was lower and the maximum binding capacity was greater in the hypertensive rats than in the control rats. The NE-stimulated phosphatidylinositol hydrolysis, estimated by measuring inositol 1,4,5-triphosphate (IP3) accumulation, was greater in the hypertensive rat artery compared with the control one. The IP3-induced contraction in the beta-escin-treated mesenteric large resistance vessel was smaller in the hypertensive rats. The vasoconstrictor response to phorbol 12,13-dibutyrate of the perfused mesenteric artery was larger in the hypertensive animals than in the control. Staurosporine antagonized the phorbol 12,13-dibutyrate-induced vasoconstriction in preparations from both rats. These results suggest that the increases in the number and affinity of alpha-1 adrenoceptors may result in an enhanced phosphatidylinositol hydrolysis accounting for an increased vascular reactivity to alpha-1 adrenoceptor agonists in deoxycorticosterone acetate-salt hypertensive rats. Furthermore, the enhancement of vasoconstrictor mechanism mediated by protein kinase C pathway may also contribute to vascular hyper-reactivity to NE, whereas the decreased IP3-induced contraction may function to minimize the hyper-reactivity observed in this model of experimental hypertension.
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PMID:Characterization of the alpha-1 adrenoceptors in the mesenteric vasculature from deoxycorticosterone-salt hypertensive rats: studies on vasoconstriction, radioligand binding and postreceptor events. 811 68

Prazosin is a selective peripheral alpha 1-adrenoceptor antagonist used in the treatment of hypertension and heart failure. This drug has the disadvantage of relatively short terminal half-life (of the order of 2 to 3 hours); its wide use has been limited by the number of daily administrations. Recently, a new formulation of prazosin has been commercialized i.e., prazosin-gastrointestinal therapeutic system (P-GITS) given once daily in doses of either 2.5 or 5.0 mg (i.e., Alpress). The potential suitability of this controlled-release system as treatment of hypertension during pregnancy seems important. However, the possible transplacental passage of PRZ was unknown. We aimed to study this phenomenon in three pregnant women given a once daily 5 mg dose of P-GITS during the third trimester of pregnancy. There is a slight transplancental passage of prazosin i.e., of the order of 10 to 20% of the maternal concentration level determined at the same time. Concerning neonatal outcome, no problems were noted and the babies left the hospital in good health. Prazosin-GITS offers a new approach to control and improve the outcome of hypertensive therapy during pregnancy.
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PMID:[Weak transplacental passage of prazosin (Alpress) during the third trimester of pregnancy. 3 cases]. 813 64

We performed these studies to assess the potential role of hemodynamic forces in mediating the changes in aortic fibronectin mRNA expression that occur in the rat in response to angiotensin II administration. With the use of an acute hypertensive model involving a 3-day infusion with a pressor dose of angiotensin II given by osmotic minipump, a selective increase in fibronectin mRNA expression but not of several other extracellular matrix genes was documented. This change was inhibited by losartan, indicating the importance of angiotensin receptors in the response. Prazosin, hydralazine, or L-arginine added to the drinking water all lowered the angiotensin II-induced increase in blood pressure but did not attenuate the increase in fibronectin mRNA expression. Angiotensin-converting enzyme inhibition using trandolapril did reduce fibronectin mRNA in the angiotensin II-infusion model, despite an inability to reduce blood pressure, whereas when angiotensin I was infused, quinapril lowered both blood pressure and fibronectin expression even at doses that did not completely normalize blood pressure. These studies suggest that angiotensin II induced an increase in aortic fibronectin mRNA that was not dependent solely on blood pressure.
Hypertension 1994 Jun
PMID:Angiotensin II alters aortic fibronectin independently of hypertension. 820 11

The present study was conducted to investigate the effect of hypertension on the formation of arterial thrombus in the rat femoral artery. The time required to establish the thrombus following endothelial injury in spontaneously hypertensive rats (SHR) was extremely prolonged. Pretreatment with prazosin which lowered the blood pressure near the level in normotensive Wistar Kyoto (WKY) rats, significantly shortened the thrombogenesis time, but it was still longer than that in WKY rats. Platelet aggregation in response to collagen with washed platelets and whole blood was reduced in SHR with and without hypotensive treatment, in comparison with that in WKY rats. Prazosin did not affect the platelet aggregability. Therefore, the decreased platelet aggregation was considered to be responsible for the delayed thrombus formation in hypotensively treated SHR. These results suggested that high blood pressure, mainly, interferes with the establishment of thrombus directly. Hypoaggregability of platelets is likely to be partly involved in the prolongation of thrombogenesis in SHR.
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PMID:Hemodynamic effects on thrombogenesis and platelet aggregation in spontaneously hypertensive rats. 846 13

Prazosin (PRZ) in conventional tablet form (P-CT) has the disadvantages of a relatively short terminal half-life, a slight solubility in water and the well-recognized adverse effect of symptomatic orthostatic hypotension. The pharmacokinetic study of a new rate-controlled formulation of prazosin (Prazosin-Gastrointestinal System: P-GS) was performed in 9 pregnant women during the third trimester of pregnancy. Patients had persistent elevation of blood pressure. The subjects gave their informed consent for oral administration of 1 daily dose of 5 mg P-GS at 8 a.m. A first analysis period on day 1 enabled definition of the initial pharmacokinetic behavior of the drug, while the aim of a second was to evaluate its fate at plateau. The clinical course of both mother and fetus was subsequently monitored. This was an open, non-randomized study, each patient serving as her own control. For 3 patients, we aimed to determine the possible transplacental passage of PRZ at delivery. PRZ levels were measured by HPLC and data were analysed by noncompartmental linear pharmacokinetic methods. The data show: (i) P-GS was well tolerated by all patients and there were no significant changes in fetal heart rate during the study. (ii) A significant decrease in diastolic blood pressure was observed after the 36th hour following the first dose of P-GS while a reduction in systolic blood pressure was observed on day 4. (iii) An approximated relative bioavailability (f'P-GS) of 36.5% was calculated. P-GS appears to have a lower bioavailability than P-CT in women of similar gestational age. (iv) Both Cmax and AUC0-->infinity are significantly increased at plateau. Further, terminal half-life is increased with regard to the value determined with P-CT. No accumulation of PRZ was noted at steady-state. (v) P-GS is an example of an oral zero-order absorption product that offers one approach to control and improve the outcome of hypertensive therapy during pregnancy. This treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension. (vi) There is a slight transplacental passage of the drug (of the order of 10-20%).
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PMID:Disposition of a new rate-controlled formulation of prazosin in the treatment of hypertension during pregnancy: transplacental passage of prazosin. 875 Oct 46

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.
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PMID:A comparative study of the reversal by different alpha 2-adrenoceptor antagonists of the central sympatho-inhibitory effect of clonidine. 882 53

The herb Scoparia dulcis L. is used in Brazilian folk medicine to treat bronchitis, gastric disorders, haemorrhoids, insect bites and skin wounds, and in oriental medicine to treat hypertension. A previous study has shown that extracts of S. dulcis have analgesic and anti-inflammatory properties; in this work the sympathomimetic activity of an ethanolic extract of Scoparia dulcis L. has been investigated in rodent preparations in-vivo and in-vitro. Administration of the extract (0.5-2 mg kg-1, i.v.) to anaesthetized rats produced dose-related hypertension blocked by the alpha-adrenoceptor antagonist prazosin (1 mg kg-1). Partition of the extract in chloroform-water yielded an aqueous phase 20 times more potent than the extract; this produced hypertension in either reserpine-treated or pithed rats. In untreated and reserpine-treated rats the same fraction (1-3 x 10(3) micrograms mL-1) produced concentration-dependent contractions of the vas deferens musculature parallel to those obtained with noradrenaline (10(-8)-10(-4)M). Prazosin (10(-7)M) reduced the maximum contractile effect of the aqueous fraction, and shifted the concentration-response curves for noradrenaline to the right. The aqueous fraction (25 and 50 micrograms mL-1) increased the inotropism of electrically driven left atria of rats, the effect being blocked by propranolol (0.4 microgram mL-1). In preparations of guinea-pig tracheal rings the aqueous fraction (1-3 x 10(3) micrograms mL-1) relaxed the muscle contraction induced by histamine (10(-4) M) in proportion to the concentration. The effect was antagonized competitively by propranolol (1.5 microM). High-performance liquid-chromatographic analysis of the aqueous fraction revealed the presence of both noradrenaline and adrenaline in the plant extract. The results indicated that both catecholamines may account for the hypertensive and inotropic effects obtained after parenteral administration of S. dulcis extracts. This sympathomimetic activity is, however, unrelated to the previously reported analgesic and anti-inflammatory properties of the plant extract, but may explain its effectiveness upon topical application in the healing of mucosal and skin wounds.
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PMID:Sympathomimetic effects of Scoparia dulcis L. and catecholamines isolated from plant extracts. 883 98

Repetitive episodic (18-24 s twice per minute) hypocapnic hypoxia (HH) administered chronically (7 h/day, 35 days) to Sprague-Dawley or Wistar-Kyoto rats results in a sustained increase in daytime blood pressure (BP). We examined acute and chronic BP response to episodic HH and eucapnic hypoxia (EH) in borderline hypertensive rats [first generation (F1) cross between spontaneously hypertensive and Wistar-Kyoto rats]. We hypothesized that episodic HH and EH would create a greater increase in acute and chronic BP in this breed of rat than in previously studied strains. We also examined neural mechanisms by which BP changes from hypoxia are induced. BP and heart rate were examined acutely in nine F1 rats during baseline, HH, EH, EH with prazosin, and EH with prazosin and atropine. Five groups of male F1 rats were studied after 35-day exposure to the following: Unhandled (n = 8): no treatment; Sham (n = 10): episodic compressed air; HH (n = 14): daily episodic hypoxia (2.7%); EH1 (n = 12); hypoxia 2.9%, CO2 8.4%; and EH2 (n = 11): hypoxia 2.8% and CO2 10.5%. Under acute conditions, HH caused a 34.2-mmHg and EH a 77.9-mmHg increase in mean BP. Prazosin partially blocked the increase in BP. Under chronic conditions, HH caused a 10.3-mmHg increase in daytime mean BP, whereas EH caused a fall in mean BP of 16.6 and 9.3 mmHg in the two separately studied groups. In the F1 rat, acute EH causes an elevation of BP but chronic EH causes a fall in BP. The acute response to EH is not predictive of what occurs after chronic exposure in the hypertension-prone F-1 rat.
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PMID:Effect of episodic eucapnic and hypocapnic hypoxia on systemic blood pressure in hypertension-prone rats. 894 33

The role of alpha 1- and alpha 2-adrenoceptors in the vascular effects of catecholamines, either released locally from sympathetic nerve endings (e.g., in vascular smooth muscle) or derived from the adrenal medulla or administered intravenously, was studied using selective antagonists of these adrenoceptors. The ganglionic stimulant dimethylphenyl-piperazinium-iodide (DMPP) exerted dual actions on blood pressure: a rapid and short-term pressor reaction (phase I) resulting from catecholamine release elicited by ganglion stimulation, followed by a more sustained blood pressure elevation (phase II) resulting from the circulating catecholamines released from the adrenal medulla. The selective alpha 2-adrenoceptor, but a not subtype selective, antagonist 7,8-(methylenedioxi)-14-alpha-alloberbane HCl (CH-38083) (50-100 micrograms/kg, IV) significantly (p < 0.05) inhibited the pressor effects of epinephrine and norepinephrine given intravenously and phase II of the DMPP-induced pressor reaction. Idazoxan exerted similar effects, but at higher doses (400-600 micrograms/kg, IV). WB-4101 (50-100 micrograms/kg, IV) and BRL-44408 (2-3 mg/kg, IV), two selective alpha 2A-adrenoceptor antagonists, had the same activity as CH-38083, except did not inhibit the pressor effect of intravenously administered norepinephrine. The alpha 2B-adrenoceptor selective antagonist, ARC-239 (150 micrograms/kg, IV) did not influence phase II of DMPP-induced pressor reaction. Prazosin (200 micrograms/kg, IV), an antagonist of alpha 1 and alpha 2B-adrenoceptors, reduced blood pressure, the pressor response to intravenously administered epinephrine, and phase I of the DMPP-induced pressor effect. In addition, it completely inhibited the pressor responses to DMPP remaining after administration of CH-38083. These results suggest that the postsynaptically located alpha 1- and alpha 2(A and B)-adrenoceptors are involved in pressor response to norepinephrine and epinephrine, and are sensitive and accessible to catecholamines released locally from the axon terminals, and from the circulation to a different extent. These results may have great therapeutical importance in hypertension, for which the involvement of both a high level of circulating and locally released catecholamines may be indicative of the usefullness of a combination (alpha 1- and alpha 2-adrenoceptors- and Ca-channel-blocking agents) therapy.
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PMID:Role of different subtypes of adrenoceptors in pressor responses to catecholamines released from sympathetic nerve endings. 897 34


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