Drugs online research references
J Vasc Res. 1995 Jul-Aug;32(4):247-53.
Functional tolerance to alpha-adrenergic receptor blockade in the spontaneously hypertensive rat highlights the multifunctional role of vascular angiotensin II in the development of hypertension.
Smid SD, Frewin DB, Wyartt CL, Head RJ.
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Treatment of spontaneously hypertensive rats (SHR) with alpha-adrenoceptor antagonists failed to alter the development of hypertension in this animal model. However, agents such as captopril (CAP) and losartan (LOS) which interfere with the renin-angiotensin system effectively prevented the development of hypertension. When tolerance occurred in the presence of doxazosin (DOX) or phenoxybenzamine, there was an enhanced sensitivity to the blood pressure lowering influence of LOS. In the presence of CAP, at a dose that did not retard the development of blood pressure in the SHR, DOX treatment significantly offset the development of hypertension in this strain. These results suggest that a functional tolerance to agents that interfere with the sympathetic nervous system is mediated by the renin-angiotensin system. Angiotensin-converting enzyme inhibition was associated with a normalization of the enhanced contraction of the mesenteric vascular bed seen in preparations from the SHR and a suppression in the development of the vascular amplifier. The results suggest that the sympathetic nervous system is unable to maintain an elevated blood pressure in the SHR during interference with the functioning of the renin-angiotensin system. Conversely, under conditions of alpha-adrenoceptor blockade, angiotensin II can maintain an elevated blood pressure in the SHR.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7654881&dopt=Abstract
Am J Hypertens. 1995 May;8(5 Pt 1):528-32.
Doxazosin lowers blood pressure and improves insulin responses to a glucose load with no changes in tyrosine kinase activity or insulin binding.
Dominguez LJ, Weinberger MH, Cefalu WT, Jacobs DB, Barbagallo M, Walsh MF, Sowers JR.
Division of Endocrinology, Wayne State University, Detroit, Michigan 48201, USA.
alpha-Adrenergic blockers have shown favorable metabolic effects. We evaluated the glucose and insulin responses to a glucose load and lipid profiles in 36 diabetic hypertensive patients before and after 8 weeks of doxazosin administration. To evaluate insulin action at the cellular level, erythrocyte insulin binding and tyrosine kinase (TK) activity were measured in 12 of these patients. Systolic and diastolic blood pressures decreased significantly (P < .0001) after 8 weeks of doxazosin therapy. Doxazosin administration significantly reduced the integrated insulin response (area under the curve [AUC]-insulin: 6093 +/- 894 to 5260 +/- 807; P = .04) and the insulin/glucose index (I/G) at 90 and 120 min after a glucose load (at 90 min, 0.230 +/- 0.055 v 0.180 +/- 0.04, P < .05; at 120 min, 0.275 +/- 0.071 v 0.173 +/- 0.036, P < .05). HDL3 level increased from 31.1 +/- 1.5 mg% to 34 +/- 1.6 mg% (P < .05) after doxazosin. Erythrocyte insulin binding and tyrosine kinase activity were not significantly altered after doxazosin. No significant correlation was found between the insulin or glucose responses and the insulin receptor binding or tyrosine kinase activity before and after treatment.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7662232&dopt=Abstract
J Cardiovasc Pharmacol. 1993 May;21(5):786-90.
Influence of alpha 1- and alpha 2-adrenoceptor antagonist therapy on the development of hypertension in spontaneously hypertensive rats.
Young RL, Jonsson JR, Mano MT, Frewin DB, Head RJ.
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
There is general agreement that the sympathetic nervous system is involved in the development of hypertension in spontaneously hypertensive rats (SHR). However, in a previous study we established that chronic administration of the selective alpha 1-adrenoceptor antagonist terazosin to SHR failed to prevent this phenomenon. In the present study, we extended that investigation further by examining the effects of another selective alpha 1-antagonist (doxazosin), an alpha 2-adrenoceptor antagonist (yohimbine), and a combination of these agents. Chronic administration of doxazosin and yohimbine produced receptor blockade, as determined by their effect on blood pressure (BP) responses to norepinephrine (NE) and phenylephrine. Chronic administration of either antagonist alone or the two in combination failed to prevent the development of hypertension in SHR, however. These findings suggest that although there may be a need for involvement of the sympathetic nervous system in the development of hypertension in SHR, its influence on this process is not mediated through activation of alpha-adrenoceptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7685450&dopt=Abstract
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