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Hypotensive Effects (hypotensive + effects)
Selected AbstractsMetabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertensionDIABETES OBESITY & METABOLISM, Issue 5 2001M. H. Uehara SUMMARY Background Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. Patients and Methods A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. Results Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54 + 1.72 to 7.54 + 1.33 mmol/l, p <,0.05), although HbA1c had decreased in both groups (PG: 6.7±3.0 to 5.9±2.6%; MG: 5.3±1.5 to 4.6±0.9%; p <,0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7±8.0 to 99.2±9.3 mmHg, p <,0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0±62.4 to 38.0±23.0 pmol/l, p <,0.05) and the insulin resistance index (3.5±2.7 to 1.8±1.0, p <,0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8±7.9 to 21.4±14.6 ,g/l; MG: 18.5±10.3 to 18.4±8.9 ,g/l). Dopamine levels increased significantly only in metformin-treated subjects. Conclusions Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels. [source] Adrenomedullin Acts in the Rat Paraventricular Nucleus to Decrease Blood PressureJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2001P. M. Smith Abstract Adrenomedullin is a recently discovered peptide involved in the control of fluid and electrolyte homeostasis and cardiovascular function through peripheral and central nervous system actions. The present study was undertaken to examine the cardiovascular effects of adrenomedullin microinjection directly into the paraventricular nucleus (PVN). Microinjection of adrenomedullin into the PVN of urethane anaesthetized male Sprague-Dawley rats resulted in site-specific, repeatable decreases in blood pressure. These hypotensive effects were found to be dose related, and were not mediated by activation of calcitonin gene-related peptide receptors. These data suggest that adrenomedullin influences cardiovascular regulation through receptor mediated actions at the PVN of the hypothalamus. [source] Natriuretic peptides in relation to the cardiac innervation and conduction systemMICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2002Magnus HanssonArticle first published online: 10 SEP 200 Abstract During the past two decades, the heart has been known to undergo endocrine action, harbouring peptides with hormonal activities. These, termed "atrial natriuretic peptide (ANP)," "brain natriuretic peptide (BNP)," and "C-type natriuretic peptide (CNP)," are polypeptides mainly produced in the cardiac myocardium, where they are released into the circulation, producing profound hypotensive effects due to their diuretic, natriuretic, and vascular dilatory properties. It is, furthermore, well established that cardiac disorders such as congestive heart failure and different forms of cardiomyopathy are combined with increased expression of ANP and BNP, leading to elevated levels of these peptides in the plasma. Besides the occurrence of natriuretic peptides (NPs) in the ordinary myocardium, the presence of ANP in the cardiac conduction system has been described. There is also evidence of ANP gene expression in nervous tissue such as the nodose ganglion and the superior cervical ganglion of the rat, ganglia known to be involved in the neuronal regulation of the heart. Furthermore, in the mammalian heart, ANP appears to affect the cardiac autonomic nervous system by sympathoinhibitory and vagoexcitatory actions. This article provides an overview of the relationship between the cardiac conduction system, the cardiac innervation and NPs in the mammalian heart and provides data for the concept that ANP is also involved in neuronal cardiac regulation. Microsc. Res. Tech. 58:378,386, 2002. © 2002 Wiley-Liss, Inc. [source] Flaxseed and Cardiovascular RiskNUTRITION REVIEWS, Issue 1 2004LeAnne T. Bloedon M.S., R.D. Flaxseed has recently gained attention in the area of cardiovascular disease primarily because it is the richest known source of both ,-linolenic acid (ALA) and the phytoestrogen, lignans, as well as being a good source of soluble fiber. Human studies have shown that flaxseed can modestly reduce serum total and low-density lipoprotein cholesterol concentrations, reduce postprandial glucose absorption, decrease some markers of inflammation, and raise serum levels of the omega-3 fatty acids, ALA and eicosapentaenoic acid. Data on the antiplatelet, antioxidant, and hypotensive effects of flaxseed, however, are inconclusive. More research is needed to define the role of this functional food in reducing cardiovascular risk [source] Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves on the cardiovascular system of anaesthetized ratsPHYTOTHERAPY RESEARCH, Issue 10 2003T. Dimo Abstract The aim of this study was to investigate the hypotensive and cardiac effects of the neutral extract from Bidens pilosa leaves. Intravenous administration of the extract resulted in a biphasic dose-related hypotensive activity. In normotensive rats (NTR), B. pilosa decreased systolic blood pressure by 18.26%, 42.5% and 30% at doses of 10, 20 and 30 mg/kg, respectively. In spontaneously hypertensive rats (SHR), the decrease in systolic blood pressure was 25.77%, 38.96% and 28.64% at the above doses, respectively. These doses induced hypotension by 27%, 34.13% and 18.73% respectively in salt-loaded hypertensive rats. In NTR, B. pilosa reduced heart rate by 23.68% and 61.18% at doses of 20 and 30 mg/kg, respectively. The force of contraction of the heart was only affected at 30 mg/kg. The initial phase of hypotensive response was partially inhibited by atropine while propranolol increased this effect. These results suggest that B. pilosa exhibited its ,rst hypotensive effects by acting on the cardiac pump ef,ciency and secondly through vasodilation. [source] Solid dispersion of rutaecarpine improved its antihypertensive effect in spontaneously hypertensive ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2008Jin-Song Ding Abstract It was reported previously that rutaecarpine produced a hypotensive effect in phenol-induced and 2-kidney, 1-clip hypertensive rats. However, the same dose of crude rutaecarpine did not produce significant hypotensive effects when applied to spontaneously hypertensive rats (SHR). In the present study, a different dose of rutaecarpine solid dispersion was administered intragastrically to SHR. The systolic blood pressure was monitored by the tail-cuff method with an electro-sphygmomanometer. The plasma concentration of rutaecarpine, calcitonin gene-related peptide (CGRP) and the mRNA levels of CGRP in dorsal root ganglion were determined. The results showed that administration of the solid dispersion significantly increased the blood concentration of rutaecarpine, accompanied by significant hypotensive effects in SHR in a dose-dependent manner. The levels of plasma CGRP were also elevated significantly, concomitantly with the increased mRNA levels in the dorsal root ganglion in a dose-dependent manner. It was concluded that a change of the dosage from the crude drug to solid dispersion could improve significantly the efficiency of rutaecarpine absorption and increase its plasma concentration. The anti-hypertensive effect exerted by rutaecarpine solid dispersion in SHR is mediated by CGRP. Copyright © 2008 John Wiley & Sons, Ltd. [source] Proarrhythmic potential of halofantrine, terfenadine and clofilium in a modified in vivo model of torsade de pointesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002Andrew J Batey This study was designed to compare the proarrhythmic activity of the antimalarial drug, halofantrine and the antihistamine, terfenadine, with that of clofilium a K+ channel blocking drug that can induce torsade de pointes. Experiments were performed in pentobarbitone-anaesthetized, open-chest rabbits. Each rabbit received intermittent, rising dose i.v. infusions of the ,-adrenoceptor agonist phenylephrine. During these infusions rabbits also received increasing i.v. doses of clofilium (20, 60 and 200 nmol kg,1 min,1), terfenadine (75, 250 and 750 nmol kg,1 min,1), halofantrine (6, 20 and 60 ,mol kg,1) or vehicle. Clofilium and halofantrine caused dose-dependent increases in the rate-corrected QT interval (QTc), whereas terfenadine prolonged PR and QRS intervals rather than prolonging cardiac repolarization. Progressive bradycardia occurred in all groups. After administration of the highest dose of each drug halofantrine caused a modest decrease in blood pressure, but terfenadine had profound hypotensive effects resulting in death of most rabbits. The total number of ventricular premature beats was highest in the clofilium group. Torsade de pointes occurred in 6 out of 8 clofilium-treated rabbits and 4 out of 6 of those which received halofantrine, but was not seen in any of the seven terfenadine-treated rabbits. These results show that, like clofilium, halofantrine can cause torsade de pointes in a modified anaesthetized rabbit model whereas the primary adverse effect of terfenadine was cardiac contractile failure. British Journal of Pharmacology (2002) 135, 1003,1012; doi:10.1038/sj.bjp.0704550 [source] Bimatoprost: A Novel Antiglaucoma AgentCARDIOVASCULAR THERAPEUTICS, Issue 2 2004D. F. Woodward ABSTRACT The aim of glaucoma therapy is to preserve vision by reducing intraocular pressure (IOP). Following recent National Eye Institute sponsored studies, it is becoming increasingly apparent that every mmHg of extra IOP lowering counts. Bimatoprost is the newest and most effective addition to the physician's armamentarium of ocular hypotensive drugs. Direct clinical comparisons have demonstrated that it is more efficacious than the prostaglandin (PG) FP receptor agonist prodrugs, latanoprost and travoprost, as well as a ,-adrenoceptor antagonist, timolol, alone or in fixed combination with the carbonic anhydrase inhibitor, dorzolamide. Moreover, patients that are refractory to latanoprost therapy may be successfully treated with bimatoprost. Such evidence provides support, at the clinical level, for the contention that bimatoprost is pharmacologically distinct from PG FP receptor agonist prodrugs. Bimatoprost is a structural analog of PGF2, -ethanolamide (prostamide F2,), which is formed from the endocannabinoid anandamide by a biosynthetic pathway involving cyclooxygenase-2 (COX-2). Their pharmacology is remarkably similar, such that bimatoprost may be regarded as a prostamide mimetic. The target receptor for bimatoprost and the prostamides appears unique and unrelated to PG- and endocannabinoid-sensitive receptors. Extensive ocular distribution/metabolism studies in non-human primates demonstrate that bimatoprost is not a prodrug, it remains essentially intact. Its profound ocular hypotensive effects may, therefore, be attributed to its prostamide-mimetic properties. [source] CHRONIC EFFECTS OF ANGIOTENSIN II and AT1 RECEPTOR ANTAGONISTS IN SUBFORNICAL ORGAN-LESIONED RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2005John P Collister SUMMARY 1.,Angiotensin (Ang) II is known to exert some of its effects centrally via circumventricular organs. These unique central nervous system areas lack the normal blood,brain barrier and, therefore, allow peptide hormones access to the brain. Of these, the subfornical organ (SFO) has been shown to be involved in many of the acute dipsogenic and pressor effects of AngII, but much less is known about the role of the SFO in the chronic effects of AngII. We hypothesized that the SFO is a central site involved in the chronic hypotensive effects of endogenous AT1 receptor blockade, as well as the chronic hypertensive effects of exogenously administered AngII. 2.,In order to test these hypotheses, SFO-lesioned (SFOx) or sham Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers for intravenous administration of losartan or AngII and continuous measurement of blood pressure and heart rate. Rats were given 3 days of saline control infusion (7 mL/day of 0.9% NaCl) and were then infused with either losartan (10 mg/kg per day) or AngII (10 ng/kg per min) for 10 days. 3.,By day 4 of losartan treatment, arterial pressure had decreased 24 ± 2 and 18 ± 2 mmHg in sham (n = 9) and SFOx (n = 10) rats, respectively. Furthermore, by day 5 of AngII infusion, arterial pressure had increased 12 ± 3 mmHg in sham rats (n = 9), but only by 4 ± 1 mmHg in SFOx rats (n = 9). In each treatment group, these attenuated pressure responses in SFOx rats continued through day 10 of treatment. 4.,These results support the hypotheses that the SFO plays a role in both the hypotensive effects of chronic AT1 receptor blockade and the chronic hypertensive phase of exogenously administered AngII. [source] | ||||||||||