摘要:

The effects of two types of repeated transient coronary artery occlusions on collateral development were examined in chronically instrumented, conscious dogs. A 2-minute coronary occlusion at 32-minute intervals (group 1, n=ll) or a 15-second occlusion at 4-minute intervals (group 2, n=7) were repeated day and night without interruption. In both groups, the total duration of coronary occlusions each day was the same (90 minutes). Before and after repetitive occlusions of either group, effects of transient 2-minute coronary occlusion on regional segment shortening in the ischemic area were examined to assess the functional state of the collateral vessels. In group 1, systolic segment shortening in the area rendered ischemic was reduced to -97.8±17.7percent; of the preocclusive control value during 2 minutes of coronary occlusion. After 125-478 repetitive occlusions (3-11 days), the degree of hypokinesia during the 2-minute occlusion was significantly improved to -0.6±4.6percent; of the preocclusive value (p<0.001 vs. before the repetition). In group 2, it remained unchanged even after 3,500-5,450 repetitive occlusions (11-16 days): -111.8±8.2percent; before and -111.4±13.8percent; after the repetition of 15-second occlusions (NS). The ratio of peripheral coronary arterial pressure to aortic pressure during transient coronary occlusion, measured by selective catheterization, was significantly higher in group 1 than in group 2 (64.4±5.3percent; vs. 20.7±1.3percent;, p<0.001). These findings suggest that myocardial ischemia of 2 minutes but not 15 seconds is vital to provide effective stimuli for angiogenesis.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Effects of quinidine, disopyramide, and procainamide on the acetylcholine (ACh)-induced K+channel current were examined in single atrial cells, using the tight-seal, whole-cell clamp technique. The pipette solution contained guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-yS, a nonhydrolysable GTP analogue). In GTP-loaded cells, not only ACh but also adenoslne induced a specific K+channel current via GTP-binding proteins (G) by activating muscarinic ACh or adenosine receptors. Quinidine and disopyramide depressed the ACh-induced K+current quite effectively. Procainamide had a weak inhibitory effect. Quinidine also depressed adenosine-induced K+current, while the effect of disopyramide on adenosine-induced current was much smaller than that on ACh-induced current. In GTP-γS-loaded cells, the K+channel was uncoupled from the receptors and was activated irreversibly, probably due to direct activation of G proteins by GTP-γS. Quinidine depressed the GTP-γS-induced K+current just as in the cases of ACh- and adenosine-induced currents of GTP-loaded cells. Disopyramide had only a weak inhibitory effect and procainamide showed no effect. From these results, it is strongly suggested that the major mechanisms underlying the anti-cholinergic effects of quinidine, disopyramide, and procainamide are different; quinidine may inhibit the muscarinic K+channel itself and/or G proteins, while disopyramide and high doses of procainamide may mainly block functions of muscarinic ACh receptors in atrial myocytes.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Disturbances in lipid metabolism may play an important role in the onset of irreversible myocardial damage. To investigate the effect of ischemia and reperfusion on lipid homeostasis and to delineate its possible consequences for myocardial damage, Krebs-Henseleit-perfused, working rat hearts were subjected to various periods of no-flow ischemia (10 to 90 minutes) with or without 30 minutes of reperfusion. During ischemia, the rise in nonesterified fatty acids (NEFAs) was preceded by the accumulation of substantial amounts of glycerol, indicating the presence of an active triacylglycerol-NEFA cycle. The subsequent rise in NEFAs (from 0.25 to 1.64 μmol/g dry residue wt after 90 minutes [means]) coincided with the reduction of ATP to values lower than 10 μmol/g dry wt and the rise of AMP, a potent inhibitor of acyl-coenzyme A synthetase, to values exceeding 2 μmol/g dry wt, making the latter compound a good candidate to hamper the turnover of endogenous lipids during prolonged ischemia. Reperfusion resulted in an additional rise in NEFAs (up to 4.1 μmol/g dry residue wt after 60 minutes of ischemia). Neither ischemia nor reperfusion resulted in significant decreases in the tissue content of triacylglycerols and the various phospholipids. During reperfusion recovery of stroke volume was still adequate at tissue NEFA levels thought to be incompatible with normal mitochondrial function.37A positive correlation (r=0.81) was found between NEFA content of reperfused hearts and cumulative release of lactate dehydrogenase during reperfusion. Accordingly it is concluded that 1) reperfusion results in additional changes in myocardial lipid homeostasis, 2) the accumulating NEFAs are compartmentalized, possibly at the cellular level, and 3) the accumulation of NEFAs is a sensitive marker for myocardial cell damage.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The objective of this study was to elucidate the mechanism by which polyamino acids containing L-arginine, L-lysine or L-ornithine cause endothehium-dependent relaxation of bovine intrapulmonary artery and vein. Basic but not acidic or neutral polypeptides ranging in average molecular weights from 17 to 225 kDa elicited tune- and concentration-dependent relaxation and cyclic GMP accumulation in precontracted rings of artery and vein by endotheh'um-dependent mechanisms. Vascular responses were markedly inhibited by oxyhemoglobin, methylene blue, or potassium. The basic polyamino acids stimulated the formation and/or release of an endothelium-derived relaxing factor (EDRF) identified as nitric oxide (NO) in perfused segments of both artery and vein as assessed by bioassay. The polyamino acids and A23187 released a similar endothelium-derived NO (EDNO) from artery and vein, as assessed by the similar half-life (3-5 seconds), antagonism by superoxide anion or oxyhemoglobin, enhancement by superoxide dismutase, and lack of influence by indomethacin. The bask polyamino acids elicited potent relaxant responses with EC50values ranging from 3±10-9to 2±10-7M, and a direct correlation was obtained between molecular weight and relaxation potency irrespective of the basic amino acid incorporated. Prolonged contact of arterial or venous rings with basic polyamino acids resulted in the rapid development of marked refractoriness to relaxation and cyclic GMP formation on addition of polyamino acid. Moreover, refractoriness developed to the vascular responses of other endothelium-dependent vasodilators but not to glyceryl trinitrate or isoproterenol. The mechanism of refractory responses was attributed to interference with EDNO formation and release as assessed by bioassay and chemical assay. The hypothesis is forwarded that the basic polyamino acids serve as partial substrates for the enzyme system that catalyzes the conversion of L-arginine to NO. Prolonged contact between substrate and enzyme results in enzyme desensitization and the development of refractoriness or a form of tolerance to vasodilators whose action is mediated by EDNO.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In rats with large myocardial infarctions, we compared the effects of captopril, a presumed arterial and venous vasodilator, with hydralazine, which is thought primarily to be an arterial vasodilator. To determine if the effects of captopril were dependent on the pathophysiological consequences of heart failure, we also studied a group of noninfarcted rats treated with captopril. In noninfarcted rats treated with captopril, left ventricular (LV) systolic and mean aortic pressures decreased from 132±12 to 107±15 mm Hg and 122±1 to 100±2, respectively (p<0.01). In noninfarcted rats, captopril decreased LV weight, LV weight/body weight, and total heart weight/body weight but produced no effects on the peripheral venous circulation. Rats subjected to coronary artery ligation were selected by ECG criteria to have large myocardial infarctions and were treated for 4 weeks with captopril (n=8), hydralazine (n=5), or placebo (n=9). In infarcted rats treated with captopril, LV systolic, mean aortic pressures and LV end-diastolic pressure (LVEDP) decreased (p<0.01) from 115±4 to 86±3 mm Hg, 106±4 to 74±3 mm Hg, and 23±2 to 11±2 mm Hg, respectively. Mean circulatory filling pressure decreased (p<0.05) from 11.2±0.6 to 8.7±0.8 mm Hg and venous compliance increased (p<0.05) from 2.04±0.07 to 2.70±0.20 ml/mm Hg/kg. Blood volume decreased (p<0.05) from 67.3±0.9 to 58.2±1.8 ml/kg. At LVEDP recorded during the hemodynamic study, LV end-diastolic volume (“operating” LV end-diastolic volume) decreased (p<0.01) from 2.64±0.15 to 1.88±0.12 ml/kg. Hydralazine treatment decreased (p<0.01) LV systolic (91±3 mm Hg) and mean aortic (86±2 mm Hg) pressures, increased (p<0.05) LVEDP (27±2 nun Hg) but did not change mean circulatory filling pressure, venous compliance, blood volume, or operating LV end-diastolic volume. We conclude that in rats with heart failure, captopril, in addition to being an arterial vasodilator, produced venodilatation and decreased blood volume. Operating LV end-diastolic volume and LVEDP were decreased. These changes appear to be caused by the decrease in blood volume and venodilatation in combination with afterload reduction because hydralazine which has no effect on the venous circulation did not alter LVEDP or operating LV end-diastolic volume.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The modulation of L-type voltage sensitive calcium channels in isolated guinea pig ventricular myocytes by the dihydropyridine (+)-202-791 was examined with the whole-cell voltage-clamp technique with 1.8 mM Ba or Ca as the charge carrier. Striking voltage- and use-dependent effects of the dihydropyridine calcium channel "agonist" (+)-202-791 were revealed. From a holding potential of -60 mV, depolarizing test pulses in the presence of (+)-202-791 demonstrated a concentration-dependent (EC50, 177 nM) increase in the measured peak inward barium current compared to control. In contrast, more depolarized holding potentials (±-30 mV) (+)-202-791 caused a biphasic effect on the peak inward current resulting in a transient enhancement followed by a steady-state block. A saturable, concentration-dependent hyperpolarizing shift in the voltage dependence of current inactivation was observed in the presence of (+)-202-791 with an EC50of 10.2 nM. The voltage dependence of current activation was also shifted in the hyperpolarizing direction in the presence of (+)-202-791. A use-dependent relative block by (+)-202-791 was observed after repetitive depolarizing test pulses at a frequency of 2 Hz. Thus, the single enantiomer (+)-202-791 can result in either an increase in the whole cell calcium channel current (favored by hyperpolarized holding potentials and low rates of stimulation) or block of calcium channel current (favored by depolarized holding potentials and high rates of stimulation). Various combinations of (-)-202-791, a reported calcium channel antagonist, and (+)-202-791 resulted in intermediate effects on voltage sensitive calcium or barium currents compared with the presence of either enantiomer alone, and no clear cooperative interactions between the enantiomers were observed in contrast to a previous single channel study (Kokuban S, Prod'ham B, Becker C, Porzig H, Reuter H: Studies on Ca channels in intact cardiac cells: Voltage-dependent effects and cooperative interaction of dihydropyridine enantiomers. Mol Pharmacol 1986; 30: 571-584). The results are discussed in relation to the possible presence of multiple dihydropyridine receptors associated with the voltage sensitive calcium channel.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Sarcoplasmic reticulum (SR) contains a Ca2+-conducting channel that is believed to play a central role in excitation-contraction coupling by releasing the Ca2+necessary for muscle contraction. The effects of calmodulin on single cardiac and skeletal muscle SR Ca2+-release channels were studied using the planar lipid bilayer-vesicle fusion technique. Calmodulin inhibited Ca2+-release channel opening by reducing the mean duration of single-channel open events without having an effect on single-channel conductance. Inhibition by calmodulin was dependent on Ca2+concentration and occurred in the absence of ATP. The effects of calmodulin were reversed by mastoparan, a calmodulin-binding peptide. Two other calmodulin antagonists [calmidazolium and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] modified the gating behavior of the channel in the absence of exogenous calmodulin in a concentration- and Ca2+-dependent manner. Our results suggest that calmodulin can modulate excitation-contraction coupling by directly interacting with the SR Ca2+-release channel of cardiac and skeletal muscle.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The left ventricular free wall (LVFW) grew approximately three times faster than the right ventricular free wall (RVFW) during the first 10 days of life in neonatal pigs. Faster growth was associated with proportional increases in total RNA and messenger RNA. These findings indicated that greater capacity for protein synthesis was a major factor in accelerated growth. Despite faster growth, heart content of ribosomal subunits was higher in piglets than in 60-day-old pigs or adult rats, suggesting a relatively slower rate of peptide chain initiation than elongation. When hearts from 5-day-old pigs were perfused in vitro, protein synthesis was more rapid in the LVFW than in the RVFW. In the absence of added insulin, the higher rate was due to both greater efficiency and greater capacity for protein synthesis. In the presence of the hormone, greater capacity was responsible for the increased rate of protein synthesis in the LVFW as compared with the RVFW.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Previous studies have shown that vasopressin potentiates the natriuresis produced by atriopeptin. In five anesthetized dogs of this study, we found that the potentiation was proportional to the dose of vasopressin infused. Sodium excretion was 46±16 μeq/min with atriopeptin (103-126) (AP24) alone (0.36 nmol/kg ± min), was increased to 127±29 by concomitant intravenous infusion of 0.4 mU/kg-mln vasopressin, was further increased to 301±75 by 1.2 μ/kg-min vasopressin and leveled off at 328±37 with 3.6 mU/kg ± min vasopressin. To investigate whether the potentiation by vasopressin was due to an intrarenal action, we infused three doses of vasopressin (0.04, 0.12, and 0.36 mU/kg±min) into the renal artery during intravenous AP24 infusion in a second group of five dogs. The natriuresis, 128±18 μeq/min, was unaffected by any intrarenal dose of vasopressin. In a third group, we determined whether the potentiation produced by vasopressin was mediated by a mechanism involving the renal nerves by denervating the left kidney before AP24 infusion. In the denervated kidneys, sodium excretion was increased from a control value of 33 ±5 μeq/min to 303 ±38 with AP24 alone and was unresponsive to subsequent intravenous vasopressin administration. The exaggerated natriuresis with AP24 alone was of the same magnitude as that produced by AP24 plus the highest doses of intravenous vasopressin in the innervated kidneys of the first group. From these results we conclude that the potentiation of AP-induced natriuresis by vasopressin is mediated by a mechanism involving the renal nerves and probably results from the known effect of vasopressin to inhibit renal nerve activity.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We tested the hypothesis that humoral or neurogenic α-adrenergic activation in the coronary circulation would produce heterogeneous vascular reactions. To accomplish this, the epicardial coronary microcirculation was viewed through an intravital microscope using stroboscopic epi-illumination. Microvascular diameters were measured under control conditions during β-adrenergic blockade (propranolol 1 mg/kg) and β-adrenergic blockade with pacing; during coronary α-adrenergic activation in the presence of β-adrenergic blockade with three doses of norepinephrine infusion (0.1, 0.5, and 1.0-2.0 μg/kg/min) or three frequencies of bilateral stellate nerve stimulation (2, 10, and 20 Hz); and during combined α- and β-adrenergic blockade (phentolamine 2 mg/kg and propranolol 1 mg/kg). Diameters of both arterial and venous vessels were reduced during β-adrenergic blockade but returned back to baseline with pacing. At the lowest level of norepinephrine infusion or frequency of bilateral stellate stimulation, microvessel constriction was not observed. At the higher doses of norepinephrine a -5.1±0.9percent; (1.0-2.0 μg/kg/min) and a -4.0±1.1percent; (0.5 μg/kg/min) decrease in diameter of arterial vessels greater than 100 μm in diameter were observed (p<0.05). At 10 Hz and 20 Hz of stellate stimulation, diameter decreased by -4.8±1.9percent; and -4.4±2.1percent;, respectively, in these relatively large vessels. Small coronary arterioles (<100/tun diameter) dilated significantly during the highest levels of nerve stimulation (9.2±2.5percent; increase in diameter) or infusion rate of norepinephrine (13.6±2.7percent; increase in diameter) (p<0.05). These constrictor and dilator responses were abolished following combined a- and β-adrenergic blockade. Norepinephrine infusion resulted in a decrease in diameter of coronary veins and venules (7.2±1.3percent;) (p<0.05), whereas stellate stimulation did not significantly reduce venous and venular diameters. In summary, the coronary venous and venular vasculature responds to α-adrenergic activation from circulating norepinephrine but is not affected by stellate stimulation. In contrast, stellate stimulation and norepinephrine infusion elicit similar responses in the coronary arterial and arteriolar microvasculature. Constriction occurs in vessels greater than 100 μm in diameter, whereas dilation predominates in vessels less than 100 μm in diameter. Such heterogeneous arterial responses would undoubtedly result in a redistribution of coronary vascular resistance toward larger coronary arteries and arterioles.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID