摘要:

The influence of selective (milrinone: 10, 50, 100 μM) and nonselective phosphodiesterase (isobutyhnethylxanthine: 0.1, 10, 100 μM) inhibitors and β-adrenergic stimulation (isoproterenol: 0.01, 0.1 μM) on phospholamban and myofibrillar protein phosphorylation was studied in guinea pig hearts perfused with [32P]orthophosphate. Changes in protein phosphorylation were compared to alterations in tissue cyclic AMP (cAMP) levels and positive inotropic effects induced by these agents. Isoproterenol (0.01 μM), milrinone (50 μM), and isobutyhnethybumthine (100 μM) all produced similar, twofold increases in dP/dt and -dP/dt but only stimulation with isobutylmethylxanthine and isoproterenol was associated with significant increases in phospholamban phosphorylation. At these equipotent doses, the effects of isobutyhnethylxanthine were associated with higher increases (3.1-fold) in cAMP than those observed with isoproterenol (twofold). Milrinone (50 μM) produced a 2.5-fold increase in cAMP levels but failed to change phospholamban phosphorylation. Higher doses of milrinone (100 μM) resulted in relatively high (4.1-fold) cAMP levels, and this was associated with increased (1.5-fold) phosphorylation of phospholamban. Phosphorylation of troponin I was significantly increased at 0.01 μM and 0.1 μM isoproterenol, while phosphorylation of C protein was observed only at 0.1 μM isoproterenol. Isobutyhnethylxanthine and milrinone did not significantly increase phosphorylation of either troponin I or C protein at any of the doses studied. These findings indicate that cardiotonic agents acting via the cAMP pathway may produce similar inotropic responses at different levels of cAMP and phosphorylation of sarcoplasmic reticulum and myofibrillar proteins.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study tests the hypothesis that capillary perfusion is controlled in groups rather than at the level of the individual capillary. We measured cell flux (using cells labeled with substituted tetramethyl rhodamine isothiocyanate, XRITC) and vessel diameter in adjoining arterioles of the terminal vasculature of hamster cremaster muscle (Nembutal, 70 mg/kg i.p.) during rest and hyperemia (10-4M adenosine). In terminal arterioles (TAs), 32 of 68 vessels showed cell flux increases from rest to hyperemia exceeding 25 times (i.e., 47% of TAs were relatively unperfused at rest). In vessels feeding TAs (TAFs), 33 of 95 (34%) were relatively unperfused at rest. Cell flux heterogeneity in TAFs decreased significantly by 27% from rest to hyperemia; the corresponding decrease (16%) in TAs was not significant. Thus, unperfused TAFs are present in a proportion which reflects capillary recruitment in hamster cremaster (Sarelius et al, Am J Physiol 1981; 241:H317) while TAs are not, and TAFs independently modulate flow distribution distally while TAs do not. The data therefore support the conclusion that TAFs control cell flow in the distal microvasculature. Analysis of normalized ranked maximal diameters showed that TAFs unperfused at rest tend to be the smaller vessels at any tissue site.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To compare the effects of hypoxia and ischemia on left ventricular (LV) diastolic function, we studied 17 isolated, isovolumic dog hearts by measuring LV diastolic chamber distensibility (LV end diastolic pressure at constant volume), wall thickness, and myocardial pH in response to hyporia at constant coronary flow or pressure versus global ischemia (zero coronary blood flow). Hypoxic perfusates consisted of methemoglobin-containing red blood cells suspended in lactated Ringer's solution. Brief cross-clamping of the coronary perfusion line was used to assess the contribution of coronary turgor to chamber distensibility and wall thickness. With hypoxia, left ventricles showed a significant early (5 minutes) decrease in diastolic distensibility and an increase in wall thickness, at either constant coronary perfusion pressure or flow. The increase in wall thickness was independent of hypoxia-induced changes in coronary turgor. In contrast, global ischemia produced an early increase in LV diastolic chamber distensibility and a decrease in wall thickness. When global ischemia was continued beyond 60 minutes, a decrease in LV chamber distensibility developed. This diastolic contracture was not associated with an increase in LV wall thickness. Myocardial pH decreased slightly during 15 minutes of hypoxia and markedly with 15 minutes of global ischemia. Thus, LV diastolic chamber distensibility decreased during 15 minutes of hypoxia, while an increase in distensibility was seen during global ischemia of similar duration. During hypoxia, these changes were associated with increased LV wall thickness, at either constant coronary perfusion pressure or constant coronary flow. Prolonged ischemia led to diastolic contracture without an increase in wall thickness. The differences in wall thickness with hypoxia versus ischemic contracture suggest differing mechanisms for these two types of diastolic dysfunction.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To determine whether the area postrema contributes to the development of hypertension in spontaneously hypertensive rats (SHR), sham or electrolytic lesions of the area postrema (AP) were made in 4-week-old SHR and Wistar-Kyoto (WKY) controls. From weeks 5 through 16, systolic pressure was measured via tail plethysmography. While blood pressure rose markedly in sham-operated SHR, increases in pressure were small in AP-ablated SHR and similar to those seen in all WKY. Subsequent direct measurements of mean arterial pressure in the same rats showed a significant correlation (r=0.87, p<0.01) with the pressure data acquired via weekly tail-cuff measurement, thereby confirming that hypertension in AP-ablated SHR had indeed been attenuated. Analysis of several hundred computer-acquired measurements of mean arterial pressure from each rat showed that AP ablation shifted the distribution of mean arterial pressure to a lower range in SHR but not WKY. Ablation of the AP also decreased resting heart rate in SHR but not WKY. Suppression of heart rate in response to intravenous phenylephrine was equivalent in sham-operated and AP-ablated rats, suggesting that baroreflex-mediated slowing of heart rate was not impaired. In response to intravenous angiotensin II, suppression of heart rate was similar in sham and AP-ablated SHR, and actually was enhanced in AP-ablated WKY. Histological evaluation of the lesions indicated that visible damage to the adjacent nuclei of the solitary tracts was confined to a small portion of the commissurel nucleus. Although we cannot rule out the possibility of damage to the remaining nuclei of the solitary tracts, gross functional damage (which would be revealed by increased lability of arterial pressure and/or decreased baroreflex sensitivity) was undetectable in the baroreflex and lability data. We conclude that ablation of the area postrema region markedly attenuates the development of hypertension in the SHR model.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effects of lysine vasopressin (LVP) on pial arteriolar diameter and cortical periarachnoid fluid prostanoid concentrations were investigated in newborn pigs. Chloralose-anesthetized piglets were equipped with closed cranial windows over the parietal cortex for observation of pial arterioles and collection of cerebrospinal fluid (CSF) passing over the cerebral surface. Prostanoids in the CSF were determined by radioimmunoassay. LVP (10-1,000 μU/ml) elicited concentration-dependent increases in pial arteriolar diameter associated with increased levels of 6-keto-prostaglandin (PG)F1α, PGE2, thromboxane B2, and PGF2α. LVP-induced pial arteriolar dilation was unchanged after intravenous indomethacin (5 mg/kg). Conversely, LVP constricts pial arterioles previously dilated by physiological (hemorrhagic hypotension) and pharmacological (topically applied PGE2or isoproterenol) intervention. This constriction is potentiated by indomethacin. Vascular and biochemical changes elicited by LVP were blocked by intravenous [l-(β-mercapto-ββ-cyclopentamethylene propionic acid), 2, (O-methyl)-Tyr-AVP] (5 μg/kg), a putative V1receptor antagonist, whereas vascular effects of norepinephrine and U46619, a thromboxane A2mimic, were unchanged. Therefore, the degree of vascular tone appears to influence responses of the newborn pig cerebral circulation to LVP.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Effects of intracellularly perfused ATP, and extracellularly applied cyanide and 2-deoxy-D-glucose, on fast and slow Ca2+channel currents of isolated single vascular smooth muscle cells were investigated by a whole-cell voltage-clamp method combined with an intracellular perfusion technique. Single smooth muscle cells were prepared by collagenase treatment from guinea pig small mesenteric arteries (diameter of <300 μm). With Cs+-rich solution in the pipette and isotonic Ba2+solution (100 mM) in the bath, depolarizing pulses evoked two types of the Ca2+channel current. Depolarizing pulses from the holding potential of -80 mV to over -30 mV evoked a fast Ca2+channel current. This fast component was inhibited by shifting the holding potential in a positive direction. With a holding potential of -40 mV, the fast component was almost inhibited. In contrast, the slow current was evoked by command potentials to above -10 mV, and its full amplitude was preserved at the holding potential of -40 mV. Without ATP in the pipette, the fast current was dominant. Increase in the ATP concentration in the pipette (0.3 to 5 mM) enhanced the slow current but did not affect the fast current. Maximum enhancement of the slow current was observed at 5 mM ATP. Increase in ATP concentration, however, did not modify the shape of the current trace and the steady state inactivation curve of the slow current. Maximum amplitudes of the fast current and slow current recorded with 5 mM ATP averaged 17.4 pA (SD of 10.4 pA, n=30; observed at -10 mV to +10 mV) and 141.8 pA (SD of 27.1 pA, n=30; observed at +30 mV to +40 mV), respectively. Presence of CN˜ and 2-deoxy-D-glucose (without glucose) in the bath, and absence of ATP in the pipette, abolished the slow current within 10 minutes; in contrast, it took more than 10 minutes to depress the fast current. The inhibitory effect of CN-and 2-deoxy-D-glucose on the slow current was reduced by intracellular application of ATP. In summary, the activation of the slow Ca2+channel required physiological concentration of ATP, whereas the fast channel current was preserved, even under ATP-free conditions. These results indicate that only the slow current is a metabolically dependent Ca2+channel current in these vascular smooth muscle cells.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study examined electrophysiological and anatomic differences between dogs with ventricular tachycardia (VT) and fibrillation (VF) inducible by programmed ventricular stimulation 7–21 days after left anterior descending coronary artery ligation. Of 106 dogs studied, 40 had inducible VT, 19 had inducible VF, and 47 had no inducible arrhythmias. Differences between these three groups of animals were examined with cardiac mapping (to determine ventricular activation time in sinus rhythm) and post-mortem pathology (to measure infarct size and to reconstruct the anatomy at the infarct edge). Animals with inducible VT had longer maximal epicardial activation time (127±8 msec) than did animals with inducible VF (91±8 msec, p<0.05) or animals with no inducible arrhythmias (75±2 msec, p<0.001). Delayed epicardial activation occurred in 90% of animals with VT, 42% of animals with VF, and in only 6% of animals with no inducible arrhythmias. Endocardial and myocardial activation times were similar for the VT and VF groups. Infarct size was 18±2% of the ventricles for the VT group, much higher than for the VF group (11±2%, p<0.001) or for the group with no inducible arrhythmias (9±1%, p<0.001). The maximum diameter of viable muscle bundles interdigitat- ing with scar tissue at the infarct edge was much larger in animals with VT (2.4±0.2 mm) than in animals with VF (1.8±0.2 mm, p<0.05) or animals with no inducible arrhythmias (1.7±0.1 mm, p<0.01). Thus, when compared with animals with inducible VF, animals with inducible VT had longer epicardial activation time, larger infarct size and viable muscle bundles of larger diameter at the infarct edge.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We have developed a micropuncture technique for the measurement of microvascular pressure in the intact lung of rabbit. We anesthetized 16 rabbits (halothane, 0.8%) and mechanically ventilated them through a tracheotomy. Then, we exposed the right lung by rib resection over the right anterior chest. We measured pulmonary artery, left a trial, and systemic pressures by direct catheterization and cardiac output by the thermodilution technique. For micropuncture, we stabilized the lung on a shelf and stopped ventilation for 3-4 minutes at an airway pressure of 7 cm H2O. We injected pancuronium intravenously to paralyze the diaphragm and intercostal muscles. Of the total pulmonary vascular pressure drop, 52% occurred in the microvascular segment between arterioles and venules of 20 μm diameter, 28% occurred in the arterial segment, and 20% occurred in the venous segment. We conclude that in the intact lung of rabbit, the major pressure drop occurs in the microvascular segment.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The recent discovery of neutral active choline and ethanolamine glycerophospholipid specific phospholipase C in myocardium (Wolf RA, Gross RW. J Biol Chem 1985; 260: 7295) has demonstrated a novel catabolic pathway that potentially contributes to the accumulation of amphiphilic metabolites during myocardial ischemia. To assess the potential importance of this pathway, we quantified the temporal course of alterations in myocardial l-0-alk-l'-enyl-2-acyl-sn-glycerol (AAG) and 1, 2-diacyl-sn-glycerol (DAG) content during control and ischemic intervals in an isolated perfused Langendorf model. AAG accumulated over fivefold to 8.70 and 18.27 nmol/g dry in 20- and 60-minute ischemic rabbit hearts, respectively (p<0.02). The only AAG molecular species that was detected in substantial amounts in control or ischemic rabbit hearts was l-0-hexadec-l'-enyl-2-acyl-sn-glycerol. Since this molecular species is enriched in plasmenylcholine these findings suggest that AAG production is likely mediated by phospholipase C-catalyzed hydrolysis of plasmenyicholine. In contrast to ischemia-induced AAG accumulation, DAG content decreased during both control and globally ischemic perfusion intervals. In summary, these findings demonstrate that AAG, in contrast to DAG, accumulates during myocardial ischemia indicating that at least some metabolites of plasmalogen and diacyl phospholipids accumulate at differential rates during myocardial ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID