Experiments were conducted on 18 dogs using an in situ blood-perfused canine heart model. Intracoronary infusion of AMP resulted in increased ATP and total adenine nucleotide levels. On reperfusion following a 15-min period of ischemia, ATP and total adenine nucleotide levels were significantly higher than control. Most important, contractile function recovered more rapidly in the AMP-treated dogs. It is therefore concluded that the delayed functional recovery noted after periods of ischemia is likely to be a direct result of delayed ATP resynthesis.
Chromosomal substitution strains afford the opportunity to discover regions of the rat genome that contain genes related to cardiovascular traits with the long-range goal of linking these genes to physiological function. PhysGen (Programs for Genomic Applications) created a consomic panel of rats derived from the introgression of a single chromosome (> or =95% of the BN chromosome, one at a time) of the Brown Norway (BN/NHsdMcwi) rat onto the homogeneous genetic background of the Dahl salt-sensitive rat (SS/JrHsdMcwi). For 3 wk before the experiment, the rats were maintained on a low-salt diet (0.4% NaCl). The dose response of aortic rings from each strain of rat to phenylephrine, acetylcholine, sodium nitroprusside, and three different levels of tissue bath hypoxia (10, 5, and 0% O2) was measured and compared with the parental SS rat. To maximize the possibility that differences among the strains would become apparent, each strain of rat including the parental SS and BN was also studied after being maintained on a high-salt diet (4.0% NaCl) for 3 wk. If the response of the aortic ring from a consomic strain to these vasoactive substances was different from that of the SS parental strain, it was concluded that the introgressed chromosome contained a gene or genes that contributed to that difference. Because the BN chromosome is removed from its native background and the SS rat loses a native chromosome, it is also necessary to consider the contribution of changes in gene-to-gene interaction.
On the isolated guinea--pig heart perfused under Langendorff preparation influence of the NO was studied. Donators of NO were nitroglycerinum and sodium nitroprusside. The myocardium contractive activity indeces and the coronary flow were studied before and after introduction of the guanilatcyclase blockade by methylene blue. The received results show that after introduction of nitroglycerinum and sodium nitroprusside myocardium contractive activity indeces decrease, and the coronary flow increases. After introduction of methylene blue myocardium contractive activity indeces almost do not change--that confirms the guanilatcyclase mechanism of NO effect.
Double sucrose gap experiments revealed differences in the effect of nitroglycerin and sodium nitroprusside on action potential and contraction of ureteral smooth muscle cells. Unlike sodium nitroprusside, nitroglycerin inhibited voltage-dependent Ca(2+) membrane permeability. It was concluded that cGMP-independent mechanisms of the effects of nitro derivative reflect the peculiarities of excitation-contraction coupling in smooth muscles.
BACKGROUND: Only a few previous studies have investigated endothelium-dependent vasodilation in the metabolic syndrome (MetS). In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to assess vasodilation in conduit and resistance arteries were evaluated in relation to the MetS and insulin resistance. METHODS: In this population-based study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. RESULTS: EDV was lower in subjects with the MetS (NECP/ATP III-criteria, prevalence 23%) compared to those without (p
The effects of the NO donor sodium nitroprusside and the NO synthase blocker L-omega-N-nitroarginine (LNA) on body temperature, hypothalamic monoamines, and plasma corticosterone in conditions of cooling were studied in Male Wistar rats. Reductions in body temperature on cooling, both after administration of sodium nitroprusside and LNA, were no different from those seen without treatment. The basal corticosterone level after treatment with sodium nitroprusside increased from 5.3 +/- 2.2 to 29.1 +/- 1.8 microg%. Cooling led to a multiple increase in corticosterone levels in all animals, both in control conditions and after treatment with sodium nitroprusside and LNA. Sodium nitroprusside significantly decreased the basal hypothalamic noradrenaline level, by 37%. Cooling of the animals in these conditions led to an additional drop in the noradrenaline level. Noradrenaline levels 48 h after cold stress applied to animals cooled after treatment with LNA or sodium nitroprusside were significantly higher than in those cooled without treatment. No changes in serotonin and 5-hydroxyindoleacetic acid levels were seen in these experiments. The basal dihydroxyphenylacetic acid and dopamine levels increased after treatment with sodium nitroprusside, by 379% and 239% respectively. No dopamine response to cold was observed, though the dihydroxyphenylacetic acid level in the control group and animals treated with LNA increased. Thus, cold stress did not reveal differently directed directions for the actions of the NO donor and the NO synthase blocker, as seen with other types of stress.
It was investigated whether the SH-groups of contractile proteins are involved in NO-induced relaxation of saponin-skinned smooth muscle strips. Both, the thiol-specific alkylating agent N-ethylmaleamide (NEM), and thiol-reducing agent dithiotreitol (DTT) induced relaxation of maximally activated skinned rat portal vein preparations. The relaxing effects of DTT and nitric oxide donor sodium nitroprusside were not additive. After the relaxation, induced by one of this agent, the effect of the other one was negligible. We suggest that NO-induced smooth muscle relaxation be due to decreasing of force sensitivity to Ca2+. This effect of nitric oxide is realized by its interaction with critical thiol groups of smooth muscle contractile proteins.
The membrane potential and smooth muscle tension in rat aorta were studied by the method of sucrose gap junction. It was found that sodium nitroprusside and nitroglycerin produced a dose-dependent membrane repolarization and smooth muscle cell relaxation in rat aorta preliminarily contracted and depolarized by hyperpotassium (40 mM) or phenylephrine solutions. The relaxation effect of sodium nitroprusside was more pronounced on the phenylephrine background. The effect of nitroglycerin showed a different kinetics in time and led to the tolerance development. The effects of both nitro compounds were inhibited by pretreatment with Methylene Blue or potassium channel blockers. It is suggested that nitro vasodilators are involved in the NO-dependent processes in smooth muscle cells of aorta through cGMP-mediated activation of the potassium conductivity and by changing the efficiency of operation of the protein kinase C branch of the Ca2+ signal system.
Heterogeneity of the cGMP-dependent contractility effects of the smooth cells (SMC) was shown in guinea pig ureter by the methods of the double sucrose gap junction. Sodium nitroprusside (SN, 0.1-100 microM) relaxed the high-K+ depolarisationprecontracted SMC but strengthened the SMC constriction triggered by electrical stimulation. In taenia coli, SN or nitroglycerin in the same concentration ranges depressed the electrical or mechanical activity of the SMC and relaxed the SMC, precontracted by depolarization in high-K+ medium. The inhibitor of the phosphodiesterases vinpocetine (1 microM) contributed to the activating effect of SN; the inhibitor of the soluble guanilatcyclase Methilen Blue (10 microM) depressed it. Histamine and mesotone (1-10 microM) increased the action potential and constriction of the SMC triggered by electrical stimulation but decreased the effect of SN. The activator of the protein kinase C (PK-C) phorbol miristoyl-13-acetyl (0.5 microM) changed direction of the SN effects inhibiting both the parameters of an action potential and of the SMC constriction. The pre-treatment with the inhibitor of PK-C calphostin C (0.1 microM) additionally depressed the effects of SN, increasing SMC constriction, especially in the presence of histamine and mesatone. We suggest that c-GMP depressed activity of the PK-C by independent mechanisms operating in SMC.
High-throughput studies in the Medical College of Wisconsin Program for Genomic Applications (Physgen) were designed to link chromosomes with physiological function in consomic strains derived from a cross between Dahl salt-sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/NHsdMcwi (BN) rats. The specific goal of the vascular protocol was to characterize the responses of aortic rings from these strains to vasoconstrictor and vasodilator stimuli (phenylephrine, acetylcholine, sodium nitroprusside, and bath hypoxia) to identify chromosomes that either increase or decrease vascular reactivity to these vasoactive stimuli. Because previous studies demonstrated sex-specific quantitative trait loci (QTLs) related to regulation of cardiovascular phenotypes in an F2 cross between the parental strains, males and females of each consomic strain were included in all experiments. As there were significant sex-specific differences in aortic sensitivity to vasoconstrictor and vasodilator stimuli compared with the parental SS strain, we report the results of the females separately from the males. There were also sex-specific differences in aortic ring sensitivity to these vasoactive stimuli in consomic strains that were fed a high-salt diet (4% NaCl) for 3 wk to evaluate salt-induced changes in vascular reactivity. Differences in genetic architecture could contribute to sex-specific differences in the development and expression of cardiovascular diseases via differential regulation and expression of genes. Our findings are the first to link physiological traits with specific chromosomes in female SS rats and support the idea that sex is an important environmental variable that plays a role in the expression and regulation of genes.