摘要:

This study investigated the mechanism of ergonovine-induced hyperconstriction of coronary artery in conscious dogs that had undergone endothelial denudation one month earlier. The diameter of the large epicardial coronary artery was continuously measured by a sonomicrometer in 12 dogs in which two pairs of 10-MHz piezoelectric crystals had been surgically implanted at the denuded and nondenuded sites of coronary arteries. A month after the endothelial denudation, intravenous ergonovine (0.01, 0.1, 0.3, and 1.0 mg) produced transient dilation followed by dose-dependent constriction. The degrees of dilation were comparable between the denuded and nondenuded sites. The magnitudes of constriction induced by ergonovine were significantly larger in the denuded site than in the nondenuded site: the percent reductions in diameter evoked with 0.3 mg ergonovine were 14.4+2.3% and 3.8±0.8% (p<0.01) at the denuded and nondenuded sites, respectively. The magnitudes of constriction induced by intravenous phenylephrine (0.02, 0.06, and 0.2 mg) were comparable in the denuded and nondenuded sites. Methysergide (a nonselective serotonergic blocker) in a dose of 0.5 mg/kg significantly inhibited vasoconstriction induced by ergonovine (0.3 mg) from 13.1±1.1% to 2.7±1.0% (p<0.01) at the denuded site and from 4.2±0.6% to 0.8±0.3% (p<0.05) at the nondenuded site. Diltiazem (1.0 mg/kg) selectively inhibited the ergonovine-induced hyperconstriction. Ketanserin (0.5 mg/kg), prazosin (1.0 mg/kg), or indomethacin (5.0 mg/kg) did not prevent the ergonovine-induced hyperconstriction. Histological study revealed intimal thickening and regenerated endothelium in the denuded site. These results suggest that the ergonovine-induced coronary hyperconstriction in our conscious canine model may be mediated by activation of serotonergic receptors with a subsequent increase in calcium influx into vascular smooth muscle cells.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To examine the relation between increased newborn oxygen requirements and the postnatal rise in cardiac output, we measured left ventricular (LV) output, organ blood flows, and whole-body oxygen consumption using radioactive microspheres in late-gestation sheep fetuses and in the same animals 1 and 4 hours after cesarean section delivery. LV output rose from 264±23 ml min−1kg body wt−1in fetuses to 444±33 ml min−1kg body wt−1in lambs at 1 hour after delivery (p<0.005) and was unchanged at 4 hours after delivery. This rise in LV output was associated with a more than fourfold increase in the LV flow contribution to tissues situated distal to the ductus arteriosus (fetus, 51±9 ml min−1kg body wt−1; lamb, 226±22 ml min−1kg body wt−1;p<0.005), which were mainly perfused by the right ventricle in utero. However, average blood flow to body tissues was similar in fetuses (37±4 ml min−1100 g tissue−1), 1-hour lambs (39±4 ml min−1100 g tissue−1), and 4-hour lambs (40±5 ml min−1100 g tissue−1). Oxygen consumption increased by 58%, from 7.84±0.43 ml min−1kg body wt−1in fetuses to 12.38±2.4 ml min−1kg body wt−1in 1-hour lambs (p<0.01), and was unchanged in 4-hour lambs. Although systemic blood flow did not change after birth, the arteriovenous oxygen content difference increased by 54%, from 1.98±0.16 ml/dl in fetuses to 3.05±0.19 ml/dl in 1-hour lambs (p<0.005), and was unaltered in 4-hour lambs. We conclude that 1) an increased LV output after birth results from the LV taking over the perfusion of tissues supplied by the right ventricle in utero, 2) the perinatal rise in LV output maintains overall systemic perfusion, 3) an increased newborn oxygen consumption is achieved through a rise in arteriovenous oxygen extraction, and 4) rises in oxygen consumption and LV output at birth are not directly related to one another.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To examine whether stimulation of α-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the c-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg · kg−1· hr−1), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the α-receptor blocker metoprolol and the α-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a α-adrenergic blocker and vasodilator with α1-blocking activity (0.5 mg · kg−1· hr−1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The β-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phospho-ribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3±1.4 units/g protein) compared with control rats (1.5±0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7±0.7 to 19.1±1.4 units/g protein. Combined α-and β-receptor blockade with carvedilol attenuated these effects. Using Northern blot analysis, we showed that G-6-PD mRNA was elevated in a time-dependent manner in hearts of NE-treated rats, reaching a 2.6-fold increase after 3 days. This increase was abolished with carvedilol. The 6-phosphogluconate dehydrogenase mRNA was only slightly and unspecifically enhanced. These results indicate that both α-and α-adrenergic receptors contribute to the stimulation of the oxidative PPP by predominant elevation of G-6-PD mRNA.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The extracellular pH (pHo) and intracellular pH (pHi) were simultaneously measured with H+-sensitive microelectrodes in the rabbit papillary muscle during normal arterial perfusion and no-flow ischemia. The preparation was kept in an artificial gaseous atmosphere (N2and CO2during ischemia) without a surrounding fluid layer. Cylindrical muscles of small diameters (< 1.0 mm) were selected to prevent major diffusion gradients of CO2within the muscle cylinder during ischemia. In normal perfusion with CO2/HCO3-buffered blood at Pco2of 35 mm Hg, pHiwas 7.03±0.03. During early ischemia, extracellular acidification was much more prominent than intracellular acidification. Consequently, the transmem-brane pH gradient reversed (pHo<pHi) at approximately 8 minutes. At 14 minutes of ischemia, pHowas 6.64 and pHiwas 6.93. A moderate increase in Pco2from 35 to 67 mm Hg before ischemia enhanced intracellular acidification in ischemia. Simulation of CO2accumulation (increase of Pco2in the surrounding atmosphere), as encountered in midmural ventricular layers during in vivo ischemia, produced a significant decrease of pHo(6.30 versus 6.64) and pHi(6.65 versus 6.93) at 14 minutes of ischemia. The presence of red blood cells in the intravascular space after arrest of coronary perfusion showed a pronounced effect on extracellular and intracellular acidosis. If the muscles were perfused with CO2/HCO3-buffered perfusate in the absence of red blood cells, the changes of pHoand pHiwere significantly larger (pHo, 6.00 versus 6.64; pHi, 6.46 versus 6.93 at 14 minutes) during ischemia. Actively developed force during ischemia was not significantly influenced by conditions modulating pHi. It decreased by 82% after 5 minutes, even when no significant change of pHiwas recorded. By contrast, ischemic contracture was dependent on intracellular acidification. It developed earlier in the absence of red blood cells or with low extracellular buffer capacity. It is concluded that during acute myocardial ischemia 1) extracellular acidification exceeds intracellular acidification, 2) the decrease in pHiis inhomogeneous because of local variation in CO2accumulation and diffusion, 3) the decrease in pHiis relatively small in the presence of red blood cells, and 4) the development of ischemic contracture but not the early decline in active tension is sensitive to changes in pHi.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The mechanisms mediating abnormal renal autoregulation in Dahl salt-sensitive (DS) rats have not been fully defined. In the present study, we assessed myogenic responsiveness of interlobular arteries (ILAs), afferent arterioles (AAs), and efferent arterioles in isolated perfused hydronephrotic Dahl rat kidneys. Dahl rats were divided into four groups according to strain (Dahl salt-resistant [DRI or DS rats) and dietary sodium manipulation (rats fed low or high salt diets). Systolic blood pressure was elevated only in DS rats fed the high salt diet (202±4 mm Hg,p<0.05). Myogenic responses were obtained by stepwise elevation of renal arterial pressure. Vessel diameters were determined by computer-assisted videomicros-copy. Preglomerular microvessels of DS and DR rats responded differently to changes in renal arterial pressure. AAs and ILAs manifested diminished myogenic responsiveness to increasing renal arterial pressure in DS rats compared with DR rats (p<0.05). Both AAs and ILAs in DS rats manifested a higher threshold pressure for eliciting myogenic responses and a decrease in maximal pressure-induced vasoconstriction. The sensitivity of the AA myogenic response to nifedipine was enhanced in DS rats compared with DR rats (p<0.05). For rats fed the high salt diet, preglomerular vessels exhibited reduced myogenic responsiveness in both strains. In contrast to preglomerular microvessels, efferent arterioles from all four groups of rats failed to exhibit pressure-induced vasoconstriction. Our data suggest that diminished myogenic responsiveness of AAs and ILAs in DS rats contributes to impaired renal autoregulation in this strain.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID