Drugs online research references
Am J Physiol. 1996 Nov;271(5 Pt 2):H2007-13.
Control of arteriovenous anastomoses in rabbit ear model of digital perfusion.
Pollock DC, Li Z, Koman LA, Gordon ES, Smith TL.
Department of Orthopaedic Surgery, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1070, USA.
The arteriovenous anastomoses (AVA) of the cutaneous microcirculation of the hands and feet are fundamental determinants of thermoregulatory blood flow and may be involved in cold intolerance. These direct microvascular studies are an initial characterization of adrenergic receptor subtypes participating in control of AVA in the ears of anesthetized male New Zealand White rabbits. Adrenergic alpha 1-stimulation with phenylephrine produced AVA constriction, whereas terazosin (an alpha 1-antagonist) produced dilation and attenuated the responses to phenylephrine. Adrenergic alpha 2-stimulation with UK-14304 produced constriction of the AVA, whereas atipamezole (an alpha 2-antagonist) produced dilation and attenuated the responses to UK-14304. When equimolar concentrations of antagonists were studied, the AVA dilation produced by alpha 2-blockade was greater than that produced by alpha 1-blockade. Norepinephrine (a mixed alpha 1- and alpha 2-agonist) also produced vasoconstriction, which was attenuated by both prazosin (an alpha 1-antagonist) and atipamezole. In summary, 1) AVA contain a heterogeneous mixture of both alpha 1- and alpha 2-receptors, and 2) alpha 2-receptors may have a greater influence than alpha 1-receptors on overall tone in AVA.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8945920&dopt=Abstract
Hypertension. 1996 Dec;28(6):1047-54.
Hypertension in obese Zucker rats. Role of angiotensin II and adrenergic activity.
Alonso-Galicia M, Brands MW, Zappe DH, Hall JE.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216, USA.
We designed our studies to determine whether blood pressure is elevated in obese Zucker rats compared with lean control rats and to test the importance of the renin-angiotensin and adrenergic nervous systems in long-term blood pressure control in this genetic model of obesity. We monitored mean arterial pressure 24 hours per day using computerized methods in 13- to 14-week-old lean and obese Zucker rats maintained on a fixed, normal sodium intake (3.3 mmol/d). Mean arterial pressure (average of 5 days) was higher in obese (100 +/- 1 mm Hg) than in lean (86 +/- 1) rats. Although control plasma renin activity was lower in obese than in lean rats (3.66 +/- 0.15 versus 5.48 +/- 0.11 ng angiotensin I/mL per hour), blood pressure sensitivity to exogenous angiotensin II was greater in obese than in lean rats. Blockade of endogenous angiotensin II receptors with losartan (10 mg/kg per day) for 7 days also caused a greater decrease in blood pressure in obese (36 +/- 2 mm Hg, n = 6) than in lean (25 +/- 1, n = 5) rats. However, combined alpha- and beta-adrenergic blockade with terazosin (10 mg/kg per day) and propranolol (10 mg/kg per day), respectively, for 8 days caused only modest decreases in blood pressure in obese (9 +/- 3 mm Hg, n = 8) and lean (4 +/- 2, n = 6) rats, despite effective alpha- and beta-adrenergic blockade. These results suggest that increased arterial pressure in obese Zucker rats depends in part on angiotensin II. However, additional mechanisms may also contribute to increased blood pressure in obese Zucker rats.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8952595&dopt=Abstract
Pharmacology. 1996 Dec;53(6):356-68.
Effects of selective and nonselective alpha-1-adrenoceptor antagonists on intraurethral and arterial pressures in intact conscious dogs.
Brune ME, Katwala SP, Milicic I, Buckner SA, Ireland LM, Kerwin JF Jr, Hancock AA.
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Ill 60064-3500, USA.
In this study, we used a novel conscious dog model to evaluate the uroselectivity of selected alpha 1-antagonists either approved for human use or in clinical development for the treatment of symptomatic benign prostatic hyperplasia (BPH) and compared those results to their in vitro binding and functional affinities at alpha 1A, alpha 1B and alpha 1D receptor subtypes. Conscious dogs were instrumented acutely with a balloon catheter for the measurement of changes in prostatic intraurethral pressure (IUP) and chronically with implantable telemetry devices for the measurement of arterial pressure. The pressor effects of the alpha 1-agonist phenylephrine (PE) on IUP and mean arterial pressure (MAP) were compared before and at various time points after oral doses of either terazosin, doxazosin, tamsulosin or Rec 15/2739 (SB 216469). At submaximal doses, terazosin and doxazosin blocked PE-induced increases in MAP to a greater extent than increases in IUP. Tamsulosin blocked both parameters equally at the lowest and highest doses; however, at the intermediate dose, IUP was blocked more than MAP. Rec 15/2739 at each dose always blocked IUP to a greater extent than MAP. While the in vivo uroselectivity of these agents was predicted by radioligand binding and in vitro functional selectivity for the alpha 1A subtype over alpha 1B and alpha 1D subtypes, results from conscious dog experiments indicate that estimates of in vivo uroselectivity also depend upon dose and the time after administration. Our conscious canine model provides the basis for frequent and repeated evaluation of uroselectivity parameters over many hours, thus providing a pharmacological profile of compound effects perhaps more relevant to clinical practice.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9032800&dopt=Abstract
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