Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Nov 1998
Propofol-induced relaxation of rat mesenteric arteries: evidence for a cyclic GMP-mediated mechanism.
Experiments were designed to evaluate whether guanosine 3',5'-cyclic monophosphate (cGMP)-mediated mechanisms contribute to vasodilation via propofol in rat mesenteric resistance arteries. Ring segments were suspended in the myograph system for isometric tension recording, and responses to propofol were tested in the presence and absence of methylene blue (MB), an inhibitor of guanylate cyclase. At concentrations > or = 1 microM, propofol caused concentration-dependent relaxation of vessel rings precontracted with U46619 (a thromboxane analog). ⋯ Furthermore, propofol (10-100 microM) increased cGMP content in cultured bovine vascular smooth-muscle cells. Soluble guanylate cyclase inhibitors, such as MB and LY83583, attenuated this effect. This investigation suggests that propofol-induced relaxations in small arteries, in addition to inhibition of calcium influx, are mediated by increases of cGMP in the smooth muscle cells.
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J. Cardiovasc. Pharmacol. · Sep 1998
Evidence for constitutive release of nitric oxide in the venous circuit of pigs.
To determine whether the venous circuit constitutively produces nitric oxide (NO), we infused the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) into anesthetized and mechanically ventilated pigs and measured venous circuit parameters. We measured cardiac output (Q) by thermodilution and obtained arterial (Part), central venous pressure (in the inferior vena cava), right atrial (Pra), pulmonary artery (PAP), and pulmonary capillary wedge pressures. A balloon was transiently inflated in the right atrium to stop venous return and obtain mean circulatory filling pressure (MCFP). ⋯ The increase in RVR of 167% from 1.8+/-0.6 mm Hg/L/min at baseline to 5.4+/-3.7 mm Hg/L/min (p < 0.05) was similar to the 188% increase in systemic vascular resistance. These data indicate that constitutive release of NO decreases baseline venous resistance and increases capacitance. There also appears to be a worsening of cardiac function when NOS is inhibited.
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J. Cardiovasc. Pharmacol. · Aug 1998
Randomized Controlled Trial Clinical TrialNoninvasive indices of autonomic regulation after alprazolam and lorazepam: effects on sympathovagal balance.
Skin conductance level (SCL) and spectral analysis of variations in heart rate (HR) and blood pressure (BP), in relation to plasma catecholamine concentrations, were used to evaluate autonomic nervous system activity during situations of supine rest within a period of 4 h after oral administration of 1 mg alprazolam and 2 mg lorazepam. Twelve healthy men received in a double-blind, randomized crossover design, either 1 mg alprazolam, or 2 mg lorazepam, or a placebo on different days. ECG, BP, respiration, and SCL were monitored continuously during each session. ⋯ Alprazolam and lorazepam had no effect on respiratory frequency. Noninvasive indices of autonomic regulation revealed several small, but significant, time-dependent effects of 1 mg alprazolam on sympathetic and parasympathetic processes, whereas for 2 mg lorazepam, these effects were less clear. The reduction in noninvasive indices of sympathetic tone after alprazolam administration corresponded with the attenuation of plasma noradrenaline concentrations by alprazolam.
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Diabetes mellitus is associated with accelerated atherosclerosis and an increased prevalence of cardiovascular disease. Although the link between diabetes and cardiovascular disease is not fully understood, loss of the modulatory role of the endothelium could be implicated in the pathogenesis of diabetic vascular complications. There is substantial evidence that vasodilatation mediated by endothelium-derived nitric oxide (NO) is impaired in animal models of diabetes and in patients with insulin-dependent and non-insulin-dependent diabetes mellitus. ⋯ Hyperglycemia-induced endothelial dysfunction may result from decreased production of NO, inactivation of NO by oxygen-derived free radicals, and/or increased production of endothelium-derived contracting factors, which oppose the protective activity of NO. This review summarizes evidence for endothelial dysfunction in diabetic patients and animals and the effects of prolonged exposure to elevated glucose in normal blood vessels and cultured endothelium. A better understanding of the mechanism(s) of hyperglycemia-induced endothelial dysfunction may unmask new preventive strategies to reduce cardiovascular morbidity and mortality in this condition.
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J. Cardiovasc. Pharmacol. · Jan 1998
Myocardial protection afforded by nicorandil and ischaemic preconditioning in a rabbit infarct model in vivo.
We previously showed that preoperative nicorandil, a hybrid potassium channel opener and nitrate compound, conferred cardioprotective effects in a hypoxia/reoxygenation model of isolated human atrial muscle by using functional recovery as an end point, and that ischaemic preconditioning surprisingly abolished the protection afforded by nicorandil. In view of this paradoxic result, this study was undertaken to assess whether ischaemic preconditioning influences any protective effect of nicorandil by using infarct size as an end point. In addition, we investigated the underlying mechanisms of the protective action of nicorandil. ⋯ Our results show that nicorandil has a protective effect against myocardial infarction in our rabbit model when infused before and during ischaemia, but not during reperfusion, and the protective effect is abolished by an ATP-sensitive potassium channel blocker. Furthermore, the addition of ischaemic preconditioning does not detrimentally influence the effect of nicorandil. This suggests that nicorandil can confer an infarct-limiting effect by opening of ATP-sensitive potassium channels with or without intermittent ischaemia, as may happen in patients with unstable angina.