Biomedical subjects

A Kitabatake

Publications and source records attributed to A Kitabatake.

At least 37 records · Page 2Linked to original sources

PubMed1992

[A case of vasovagal syncope associated with venipuncture].

A 33 year-old-man presented recurrent syncopal episodes after venipuncture. This was sometimes associated with seizure. It was also noted that the syncope was aroused by mental stress. The patient was admitted to the department of neurological medicine because of epilepsy. Cardiac arrest of more than 15 seconds was detected during the venipuncture-prooshed syncope test. He had normal routine testing, holter monitoring, head CT scan, carotid sinus massage, valsalva maneuver etc. The syncope was similar to a malignant vasovagal one which has no typical warning signs. He had recurrent syncopal episodes without typical prodrome. Therefore a DDD pacemaker was implanted. It has not been completely established as effective in the treatment of vasovagal syncope, but for the treatment of syncope involving cardioinhibitory action, dual chamber pacing in considered as the main treatment available.

Adult↗

PubMed1991

Pulmonary venous flow velocity pattern as assessed with transthoracic pulsed Doppler echocardiography in subjects without cardiac disease.

Pulmonary venous flow velocity pattern (PVFVP) was analyzed in 53 subjects (aged 25 to 77 years, mean 47) without cardiovascular disease who underwent transthoracic pulsed Doppler echocardiography. The forward flow velocity pattern was biphasic in 37 of the 53 subjects, with each of the 2 peaks in systole and diastole; flow was triphasic with 2 peaks in systole and the other peak in diastole in the remaining 16 subjects. Peak systolic and diastolic flow velocity ranged from 28 to 84 cm/s and from 27 to 71 cm/s, respectively. Mean systolic flow velocity was significantly greater than mean diastolic flow velocity (53 +/- 12 vs 47 +/- 11 cm/s, p less than 0.01). Systolic flow velocity and the ratio of systolic to diastolic flow velocity increased and diastolic flow velocity decreased with aging (r = 0.52, p less than 0.001, r = 0.70, p less than 0.001 and r = -0.49, p less than 0.001, respectively). Reverse flow occurred during the atrial contraction phase and its velocity (mean 20 cm/s) increased with aging (r = 0.56, p less than 0.001). The parameters of PVFVP were compared with the ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio) measured in the transmitral flow velocity pattern. As E/A ratio increased, systolic flow velocity and systolic/diastolic flow ratio and peak reverse flow velocity decreased (r = -0.40, p less than 0.01, r = -0.67, p less than 0.001 and r = -0.68, p less than 0.001, respectively) and diastolic flow velocity increased (r = 0.58, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

The effect of beta-adrenergic blockade in dilated cardiomyopathy--a questionnaire study in Japan.

The effect of beta-blockade in dilated cardiomyopathy was studied by a questionnaire survey. Thirty-three cases were monitored in whom metoprolol (22 patients, 35.9 +/- 20.4 mg, mean +/- SD), propranolol (four patients, 26.3 +/- 7.5 mg), or other beta-blockers (seven patients) were administered. Four patients died, but no direct relationship was found between administration of beta-blocker and death. The NYHA functional class improved significantly. The mean heart rate decreased from 96/min to 77/min (P less than 0.01). The mean cardiothoracic ratio decreased from 55.6% to 52.1% (P less than 0.01). The mean ejection fraction of the left ventricle measured by echocardiogram increased from 30.4% to 36.9% (P less than 0.01). Exercise tolerance in the treadmill test improved significantly. There was no change in blood pressure, nor were there arrhythmias seen on Holter electrocardiograms. In two patients, congestive heart failure deteriorated after administration of beta-blockers. It is concluded that beta-adrenergic blockade has a beneficial effect in most of the patients with dilated cardiomyopathy.

Adolescent↗

PubMed1991

Detrimental effects of beta-adrenergic stimulation on beta-adrenoceptors and microtubules in the heart.

Increased plasma catecholamines - in particular, excessive beta-adrenoceptor activation in chronic heart failure - may easily desensitize the beta-adrenoceptors as well as the postreceptor signal transductions. Since these detrimental changes in the failing heart could be reversible, administration of low-dose beta-blocker, which minimizes the negative inotropic effects, may be effective in attenuating the harmful effects of sympathetic nerve activation. Beta-adrenoceptor stimulation may also produce microtubule disruptions of the cell either through direct action or through an increase in heart rate. Treatment with beta-blockers could attenuate Ca overload by slowing the heart rate and may be useful as a protection from the structural disintegration of the cell. Thus, to clarify the underlying mechanisms of beta-blocker therapy for chronic heart failure, we have to consider not only to the functional aspects but also to the structural changes of the cells.

Adrenergic beta-Antagonists↗

PubMed1991

Transcardiac alteration of neutrophil function before and after coronary thrombolysis in human myocardial infarction.

We examined function of isolated neutrophils taken from aorta and coronary sinus before and after thrombolytic reperfusion in 17 patients whose infarct-related coronary arteries were totally occluded. Before reperfusion in left coronary artery disease, free radical generation by activated neutrophils in coronary sinus, assessed by ferricytochrome c reduction (phorbol myristate acetate, 10 ng/ml) and luminol-enhanced chemiluminescence (A23187, 2 microM), was reduced by 20% (P less than 0.05) and 30% (P less than 0.05), respectively, compared with those in aorta. Neutrophil aggregation (A23187, 10 microM) and chemotactic activity (formyl-methionyl-leucyl-phenylalanine, 5 microM) were also reduced in coronary sinus by 21% and 20%. After reperfusion the extent of such neutrophil function in coronary sinus recovered and was similar to that in aorta. There were no significant differences between neutrophil counts in aorta and coronary sinus before and after reperfusion. In right coronary artery disease, no significant changes were seen in these functions of neutrophils of aorta and coronary sinus before and after reperfusion. These results indicate that function of neutrophils passing through coronary circulation fluctuated significantly in association with reperfusion, suggesting (1) factor(s) that depress neutrophil function are produced in coronary circulation during myocardial ischemia and their effects are overcome after reperfusion or (2) activated neutrophils, trapped in the ischemic coronary bed, are washed out to coronary sinus after reperfusion.

Chemotaxis, Leukocyte↗

PubMed1991

Effects of coronary angioplasty on left ventricular diastolic filling in patients with old myocardial infarction: a study with pulsed Doppler echocardiography.

To examine the effects of percutaneous transluminal coronary angioplasty (PTCA) on left ventricular diastolic filling in patients with an old myocardial infarction, transmitral flow velocity pattern was measured using pulsed Doppler echocardiography before and after PTCA for the peak early diastolic filling velocity (E) and the ratio of the early diastolic filling to peak atrial filling velocities (E/A ratio) in 73 patients with coronary artery disease. These patients were classified into three groups: 34 patients without previous myocardial infarction (no MI group), 16 patients with an old myocardial infarction in whom a non-infarct-related vessel was reperfused by PTCA (MI-1 group), and 23 patients with an old myocardial infarction in whom the infarct-related vessel was reperfused by PCTA (MI-2 group). The degree of improvement in left ventricular diastolic filling was calculated using the values before PTCA as controls. The % increases in E and E/A ratio were 20 +/- 15 and 25 +/- 19%, respectively, in the no MI group and 27 +/- 20 and 18 +/- 16%, respectively, in the MI-1 group and there was no significant difference between these groups. The % increases in E and E/A ratio in the MI-2 group were 7 +/- 19 and 6 +/- 17%, respectively, and were significantly (P less than 0.05) less than those in the no MI and MI-1 groups. An increase in E, E/A ratio or both by 20% or more was observed in 21 of the 34 (62%) patients of the no MI group, in 10 of the 16 (63%) patients of the MI-1 group and in six of the 23 (26%) patients of the MI-2 group. Thus, reperfusion of a non-infarct-related vessel in patients with an old myocardial infarction improves left ventricular diastolic filling to the same degree and with the same frequency as in patients without myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Alterations of intracellular calcium homeostasis and myocardial energetics in acute adriamycin-induced heart failure.

To elucidate the mechanism of acute contractile failure induced by adriamycin, the intracellular concentrations of free calcium ([Ca2+]i) and energy-related phosphate compounds were determined in isolated ferret hearts. The time-averaged [Ca2+]i was measured at 10 min resolution using fluorine nuclear magnetic resonance (NMR) spectroscopy and the NMR-sensitive Ca2+ indicator 5F-BAPTA. [Ca2+]i significantly increased from a control of 381 +/- 66 nM (mean +/- SEM, N = 5) to 789 +/- 171 nM during 30 min of perfusion with adriamycin (30 mg/L), and remained elevated for at least 30 min after washout. The isovolumic LV pressure decreased to 80.7 +/- 8.9% of control (N = 12, p less than 0.05) and did not recover after washout. Intramyocardial contents of energy-related phosphates were determined by phosphorus NMR spectroscopy in seven other hearts. No significant change in myocardial energy metabolism was observed during adriamycin exposure and after washout; inorganic phosphate did not increase, and phosphocreatine and ATP did not decrease. These results indicate that Ca overload induced by adriamycin is associated with acute contractile failure. Adriamycin has been reported to inhibit Na-Ca exchange and to affect the gating of Ca2+ release channels in sarcoplasmic reticulum. Whatever the cause of the calcium overload, the fact that dysfunction persists as an aftereffect of adriamycin is consistent with the hypothesis that calcium overload, in the absence of ischemia, can leave behind long-lasting contractile dysfunction.

Adenosine Triphosphate↗

PubMed1991

Role of increased alpha 1-adrenergic activity in cardiomyopathic Syrian hamster.

We investigated serial changes in myocardial norepinephrine content and myocardial adrenergic receptors during the development of cardiomyopathy in Syrian hamsters (Bio 14.6) and their age-matched healthy controls. We also examined phosphatidylinositide hydrolysis after alpha 1-adrenergic stimulation and the effects of alpha 1-blockade. We found that in the prehypertrophic stage, myocardial norepinephrine content and densities of alpha 1- and beta-adrenergic receptors were significantly higher in the cardiomyopathic hamsters than in the controls. However, in the early heart failure stage, beta-receptor density was 28% lower than that of the age-matched controls, although alpha 1-receptor density remained 55% higher. Norepinephrine-stimulated phosphatidylinositide hydrolysis in the cardiomyopathic hamster in the hypertrophic stage was twice that in the controls, indicating that the increase in alpha 1-adrenergic receptors is coupled with the intracellular signal transduction. Furthermore, selective alpha 1-adrenoceptor blockade by bunazosin in the cardiomyopathic hamsters from 70 to 170 days of age reduced myocardial hypertrophy and focal myocardial necrosis. Thus we conclude that increased alpha 1-adrenergic activity plays an important role in progression of cardiac hypertrophy is cardiomyopathic Syrian hamsters.

Adrenergic alpha-Antagonists↗

PubMed1991

Positive inotropism in hypothermia partially depends on an increase in maximal Ca(2+)-activated force.

We investigated the contribution of maximal Ca(2+)-activated force to the positive inotropism induced by mild hypothermia. Phosphorus-31 nuclear magnetic resonance spectroscopy revealed that neither energy-related phosphorus compounds in myocardium nor intracellular pH was responsible for the change in contractility. Maximal Ca(2+)-activated pressure (MCAP), the intact-heart correlate of maximal Ca(2+)-activated force, was determined in isolated perfused rabbit hearts by measuring isovolumic left ventricular pressure during tetani at extracellular Ca2+ concentrations greater than or equal to 10 mM. Tetani were elicited by rapid pacing after exposure to ryanodine. MCAP increased by 2.17 +/- 0.28% (mean +/- SE, P less than 0.001, n = 19) for each degree of myocardial cooling between 30 and 38 degrees C. Our results indicate that a primary change in myofilament Ca2+ responsiveness underlies the positive inotropism in hypothermia. The increase in maximal Ca(2+)-activated force may explain the observation of positive inotropism without an upward shift in the relation between oxygen consumption and pressure-volume area, as previously reported for cooled whole hearts.

Animals↗

PubMed1991

Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization.

BACKGROUND: Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS: To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS: We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Allopurinol↗

PubMed1991

Staged reperfusion attenuates myocardial stunning in dogs. Role of transient acidosis during early reperfusion.

BACKGROUND: Acidosis during early reperfusion is reported to be beneficial for myocardial stunning. We tested in 31 dogs the hypothesis that staged reperfusion is beneficial to myocardial stunning. METHODS AND RESULTS: Contractile dysfunction was observed 3 hours after the onset of reperfusion after 15 minutes of occlusion of the coronary artery. In the staged reperfusion, pH of the coronary venous blood was lower for 20 minutes and fractional shortening was significantly improved compared with the control reperfusion group. When we increased pH of the reperfused myocardium by an intracoronary infusion of sodium bicarbonate, beneficial effects of the staged reperfusion were abolished. Furthermore, an intracoronary infusion of hydrogen chloride, which mimicked the changes in pH in coronary venous blood of the staged reperfusion, attenuated myocardial stunning. CONCLUSIONS: These results indicate that acidosis during staged reperfusion primarily attenuates myocardial stunning. This procedure is clinically applicable for attenuation of reperfusion injury.

Acidosis↗

PubMed1991

Delayed end ejection increases isovolumic ventricular relaxation rate in isolated perfused canine hearts.

We sought to determine the ejection variables that are principally responsible for increases in isovolumic ventricular relaxation rate observed with increases in stroke volume. In nine isolated canine hearts, left ventricular ejection was controlled by patterns specially designed to isolate the ejection parameters most critical to isovolumic relaxation rate. When stroke volume was augmented by increases in end-diastolic volume (EDV) with end-systolic volume (ESV) held constant, isovolumic ventricular relaxation rate was unchanged, as gauged by the time constants of single-exponential fits to decaying pressure. In contrast, when ESV was decreased with EDV held constant, isovolumic relaxation time constants decreased significantly, from approximately 100 to 70 msec (protocol I). The important difference in these two situations might have been that the time of end ejection was delayed in the case with faster isovolumic relaxation. To rule out other parameters that may have influenced isovolumic relaxation, ejection velocity was varied in another protocol (protocol II) by either delays in time of the onset of ejection or advances in end-ejection time, always with constant ESV and EDV. Here isovolumic relaxation was progressively slowed as end ejection occurred earlier, whereas isovolumic relaxation rate was insensitive to changes in the onset of ejection, consistent with the unique importance of end ejection to isovolumic relaxation. In fact, our analysis reveals the remarkable finding that changes in isovolumic relaxation time constant produced by either protocol I or protocol II could be related quantitatively to end ejection by a single curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Beneficial effects of alpha 1-adrenoceptor activity on myocardial stunning in dogs.

This study was undertaken to elucidate whether alpha-1 adrenoceptor activity is beneficial to contractile dysfunction during reperfusion after a brief period of ischemia (stunned myocardium) in 54 open-chest dogs. Contractile dysfunction assessed by fractional shortening (FS) was observed 3 hours after the onset of reperfusion following 15 minutes of complete occlusion of the left anterior descending coronary artery. Pretreatment with prazosin (4 micrograms/kg/min i.c.) further deteriorated contractile dysfunction compared with the untreated condition (12.7 +/- 0.6% versus 6.9 +/- 0.4% with prazosin treatment, p less than 0.001). Conversely, alpha 1-adrenoceptor agonists, methoxamine (1.0 microgram/kg/min i.c.) and norepinephrine (0.24 microgram/kg/min i.c.) with rauwolscine and propranolol, significantly attenuated contractile dysfunction (FS in the methoxamine-treated group, 17.3 +/- 0.3%, p less than 0.001 versus the untreated group; FS in the norepinephrine-treated group, 18.0 +/- 0.9%, p less than 0.05 versus 13.6 +/- 1.1% in the propranolol group). Both adenosine release and hyperemic coronary flow response during the early reperfusion period were significantly attenuated in the prazosin-treated group, and both were enhanced in the alpha 1-adrenoceptor stimulation groups. These results suggest that beneficial effects of alpha 1-adrenoceptor activity may be due to the enhanced release of adenosine. To test the cause-effect relation between the extent of adenosine release and contractile dysfunction during reperfusion, 8-phenyltheophylline was infused to block adenosine receptors in the methoxamine-treated group. The treatment with 8-phenyltheophylline completely abolished (FS, 7.4 +/- 0.3%) the beneficial effect of the enhanced adenosine release by alpha 1-adrenoceptor stimulation. Furthermore, in the prazosin-treated group, adenosine (9 micrograms/kg/min) was additionally infused into the left anterior descending coronary artery 5 minutes before and 2 hours after the onset of reperfusion. Both hyperemic coronary flow and contractile dysfunction (FS, 17.3 +/- 0.3%) recovered to the levels of the alpha 1-adrenoceptor stimulation groups. However, treatment with papaverine could not prevent deleterious effects of prazosin despite the fact that comparable hyperemic flow was obtained. Instead, lactate production up to 10 minutes after the onset of reperfusion was significantly larger (p less than 0.01) despite augmented contractile function in the prazosin-treated and the 8-phenyltheophylline with methoxamine-treated groups compared with the untreated group. The electron microscopic examination revealed no irreversible myocardial injury with and without pharmacological interventions. Thus, we conclude that alpha 1-adrenoceptor activity can reduce the magnitude of myocardial stunning and that its cellular mechanism is due to enhanced adenosine release by alpha 1-adrenoceptor activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

PubMed1991

Endogenous adenosine inhibits platelet aggregation during myocardial ischemia in dogs.

The goal of this study was to clarify that blockade of adenosine receptors during myocardial ischemia causes further reductions in coronary blood flow due to platelet aggregation. Coronary perfusion pressure in 47 open-chest dogs was reduced such that coronary blood flow decreased to one fifth of the control value; thereafter, coronary perfusion pressure was maintained at the low levels. During hypoperfusion, coronary flow was kept low but constant with a massive release of adenosine. When 8-phenyltheophylline, an adenosine receptor antagonist, was infused during coronary hypoperfusion, coronary blood flow (18 +/- 2 ml/100 g/min) gradually decreased at 5-10 minutes of ischemia and reached almost zero at 20 minutes. Three minutes after the onset of ischemia, before further reduction of coronary flow, the microscopic examination revealed the existence of thromboembolization in the small coronary arteries, and the number of platelets in the regional coronary venous blood were significantly decreased, indicating that a further reduction of coronary flow due to treatment with 8-phenyltheophylline is attributed to thromboembolism caused by platelet aggregations. This reduction of coronary flow and formation of thromboembolism were inhibited by the treatments with dibutyryl cAMP, forskolin, and yohimbine, indicating that this thromboembolization during a lack of adenosine activity is due to platelet aggregation and that platelet aggregation caused by 8-phenyltheophylline is triggered by stimulation of alpha 2-adrenoceptors by released norepinephrine during ischemia. We demonstrate that adenosine, generated endogenously in response to ischemia, inhibits platelet aggregation. The finding that adenosine is not merely a vasodilator but that it also regulates thrombosis has major implications for designing new strategies of myocardial salvage.

Adenosine↗

PubMed1991

Neutrophil-induced myocardial cell damage and active oxygen metabolites.

Free radicals derived from polymorphonuclear leukocytes (PMN) have been suggested to play an important role in myocardial ischemia-reperfusion injury. To define the mechanism by which activated PMN exacerbate ischemic myocardial damage, we investigated the extent of cell injury, free radical generation and lipid peroxidation in embryo mouse myocardial cells co-incubated with activated PMN. The generation of free radicals derived from PMN correlated with the extent of myocardial cell injury. Among the cell sheets preconditioned with hypoxic and glucose free medium, PMN-adhered myocardial cells were initially injured after adding PMN activator, extending to adjacent cells. Chemiluminescence emission and thiobarbituric acid reactive substance in the co-incubated cells were markedly increased and sustained compared with those in each cell monoincubation. The augmented lipid peroxidation was related to the progression of myocardial cell injury. These results indicate that PMN-derived free radicals cause membrane disruption, contributing to the progression of myocardial injury.

Animals↗

PubMed1991

[Quantification of mitral regurgitation by Doppler color flow mapping: comparison of mitral regurgitant fraction and volume with Doppler measurements].

Color flow imaging of the regurgitant areas has been used to quantitate the severity of valvular regurgitation, however, the exact relationship between color flow areas and regurgitant volumes or fraction has not been clarified. This study was designed to determine whether measurements of jet flow areas and distances using color flow imaging are closely related to the regurgitant volume (MRV:ml/beat) and fraction (MRF: %). Doppler examinations were performed in 29 patients with mitral regurgitation (MR). The MR jet was depicted as the largest clearly definable flow disturbance on the echo images, and the maximal jet area (cm2) and length (cm) were measured. The MRV and MRF were obtained from the Doppler measurements of the transmitral flow (TMF) and the aortic flow (AF) as follows: MRV = TMF-AF, MRF = MRV/TMF x 100. The maximal jet area showed significant correlations with the MRV and MRF (r = 0.75 and 0.75, p < 0.01), and the maximal jet length showed even better correlations with the MRV and MRF (r = 0.82 and 0.80, p < 0.01), irrespective of the etiology of MR. Thus, both the maximal jet area and length obtained from color flow imaging can be simple and useful measurement methods for predicting the MRV and MRF.

Blood Flow Velocity↗

PubMed1991

[Clinical significance of I-123 MIBG myocardial scintigraphy for evaluating the severity of congestive heart failure].

We studied the significance of I-123 MIBG (metaiodobenzylguanidine) myocardial scintigraphy for evaluating the severity of congestive heart failure. I-123 MIBG scintigraphy was performed in 7 patients with congestive heart failure (CHF) of NYHA class I-III (6 with dilated cardiomyopathy and 1 with Adriamycine cardiomyopathy) and in 2 normals. The SPECT and anterior planar myocardial images were obtained 15 minutes after (initial images) and 4 hours after (delayed images) an injection of I-123 MIBG (111 MBq). Compared with normals, patients with CHF demonstrated (1) low myocardial uptake and (2) rapid myocardial washout of I-123 MIBG, indicating myocardial sympathetic disarrangement. Then, quantitating these abnormalities with the heart to upper mediastinum uptake ratio (H/B) and the percent washout rate (%WR) during 4 hours, respectively, we compared these two indices with LV ejection fraction (EF) at rest measured by echocardiography and exercise capacity (max VO2 and VO2 at anaerobic threshold (AT] determined with respiratory gas exchange analysis during maximal bicycle exercise. H/B was lower and %WR was greater in patients with CHF than in normals. H/B correlated with EF (r = 0.77, p less than 0.05) and AT (r = 0.74, p less than 0.05). On the other hand, %WR significantly correlated with EF (r = 0.79, p less than 0.05), max VO2 (r = -0.74, p less than 0.05) and AT (r = -0.81, p less than 0.05). Thus, H/B and %WR were closely related to the severity of CHF. These results suggest that I-123 MIBG myocardial scintigraphy and the quantitative analysis of I-123 MIBG myocardial uptake provide useful information about the severity of CHF.

3-Iodobenzylguanidine↗

PubMed1990

Alpha 1-adrenoceptor stimulation increases intracellular pH and Ca2+ in cardiomyocytes through Na+/H+ and Na+/Ca2+ exchange.

The effects of alpha 1-adrenergic stimulation on intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were investigated in isolated rat cardiomyocytes with fluorescence dyes, BCECF and fura-2, respectively. In the presence of 5 or 25 mM HCO3- norepinephrine (NE) increased pHi in a dose-dependent manner. Intracellular alkalinization was inhibited by prazosin and phentolamine but not by yohimbine. NE-induced alkalinization was inhibited in the presence of a Na+/H+ exchange inhibitor (5-(N,N-hexamethylene) amiloride (HMA)), a C kinase inhibitor (H-7) or a calmodulin inhibitor (W-7), or in the absence of extracellular Na+. NE also increased [Ca2+]i following the pHi increase, which was abolished in the absence of extracellular Na+ or Ca2+. This Ca2+ influx was inhibited by HMA but not by diltiazem (10(-5) M). Thus, we conclude that alpha 1-adrenergic stimulation enhances Na+/H+ exchange by activation of C kinase, thereby allowing intracellular alkalinization, and that subsequent activation of Na+/Ca2+ exchange increases Ca2+ influx.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗