丹参制剂对豚鼠心室乳头肌电生理活动的影响(英文)

本实验通过标准玻璃微电极技术和微机系统的实时应用,利用异丙肾上腺素(ISO)制备心肌损伤的动物模型,观察丹参制剂对正常和异丙肾损伤性豚鼠心室乳头肌动作电位的影响。结果表明:①ISO使RP、APA、OS显著降低,APD明显延长,Vmax略有下降,但变化不明显。②丹参可使受损伤心肌动作电位的APD缩短而其它指标不变。③丹参在最大有效浓度(0.25mg/ml)时,可使正常豚鼠乳头肌快反应动作电位的APD缩短,而对RP、APA、Vmax基本无影响。④丹参使慢反应动作电位的APA、APD和Vmax减小。提示:丹参可能为钙桔抗剂,并能对抗ISO引起的心肌钙超载性损伤。     

Subtypes of adrenergic receptors and intracellular mechanisms involved in modulatory effects of noradrenaline on glutamate

We have previously reported that the response of cultured chick cerebellar neurons to glutamate is enhanced by noradrenaline (NA) or isoproterenol and suppressed by clonidine. The present study was carried out to further specify the adrenergic receptor subtypes involved in the facilitatory effect of NA or isoproterenol and the suppressive effect of clonidine, and to examine the intracellular mechanisms underlying these modulatory effects of NA. The clonidine effect, which was mimicked by NA iontophoresed with large ejecting currents, was blocked by yohimbine and tolazoline (alpha 2 antagonists) and also by dibutyryl cyclic AMP or forskolin which augmented the glutamate response by itself. Prazosin, an alpha 1 receptor antagonist did not block the clonidine effect. NA- or isoproterenol-induced facilitation, which was mimicked by denopamine (beta 1 agonist), was antagonized by acebutolol (beta 1 antagonist) and not by ICI 118,551 (beta 2 antagonist). Pretreatment of neurons with pertussis toxin for more than 24 h blocked the suppressive action of clonidine without affecting the facilitatory action of isoproterenol. Furthermore, intracellular injection of GDP beta S inhibited the modulatory effects of either clonidine or isoproterenol. These results indicate that the facilitatory and inhibitory modulatory effects of NA may be mediated by beta 1 and alpha 2 receptors linked to cAMP systems, respectively, and the former is coupled with the stimulatory G protein (Gs) and the latter is with the inhibitory G protein (Gi).     

Effect of fish oil pretreatment on isoproterenol-induced changes in myocardial membrane phospholipids

OBJECTIVE: In the present study, the protective effect of fish oil treatment on the fatty acid composition in isoproterenol (IPH)-induced myocardial infarction was studied in male albino Wistar rats. METHODS: Rats were injected for 2 consecutive days with IPH (60 mg/kg body weight) at 24-h intervals to induce myocardial infarction. Fish oil was administered orally at a dose of 0.05 mL/d for 45 d, after which serum and heart tissue were assayed for lipid profile, lipoprotein changes, and myocardial membrane phospholipid fatty acid composition. RESULTS: Biochemical assessment of myocardial infarction was done by measuring the activities of creatinine kinase and lactate dehydrogenase, which were significantly elevated in the rats administered with IPH. Further, the administration of IPH modified the fatty acid composition and analysis of fatty acids showed there was an increase in the omega-3/omega-6 ratio in phospholipid pool. In addition, increased levels of total cholesterol, free cholesterol, ester cholesterol, phospholipids, triacylglycerols and free fatty acid was observed in serum and heart tissue of IPH-induced rats. The fish oil treatment for a period of 45 d decreased the levels of cardiac markers (creatinine kinase and lactate dehydrogenase) and reversed the biochemical lesions induced by IPH. CONCLUSION: Our study suggests that fish oil treatment has a hypolipidemic effect and has potential use in the treatment of myocardial infarction.     

In vivo alpha 2-adrenoceptor-mediated inhibition of isoproterenol-stimulated free fatty acid output in dog bone marrow adipose tissue

Clomdine, an α₂ agonist, inhibited the isoproterenol-induced free fatty acid outflow from perfused bone marrow adipose tissue of dog tibia. This effect was suppressed by the α₂-antagonist, yohimbine. These in vivo experiments clearly demonstrate an α₂-adrenoceptor-mediated inhibition of isoproterenol-induced lipid mobilization and argue for a physiological interplay between β- and α₂-site stimulation in the regulation of lipolysis.     

Effect of isoproterenol on blood pressure, plasma renin activity, and water intake in rats

The effects of s.c. administered isoproterenol on blood pressure, plasma renin activity and water intake were studied in unanaesthetized rats as a function of both concentration and time. Isoproterenol (1, 10, 100 and 500 μg/kg) induced a rapid, dose-related decrease in blood pressure and increase in plasma renin activity. Both parameters were found to be nearly normal after 60 min, except after the highest dose. Isoproterenol (? 10 μg/kg) caused a dose-dependent increase in water intake; after the highest dose 5–6 mlH₂O/100 g b.w. was ingested within 60 min. In rats on a sodium-deficient diet, the effect of isoproterenol on renin release and water intake was potentiated whereas in DOCA-pretreated rats, the effect was inhibited. The different actions of isoproterenol, 100 μg/kg were blocked by propranolol, partly (0.5 mg/kg) or completely (2.5 and 10 mg/kg). The results indicate that the action of isoproterenol on water intake is correlated with its ability to induce renin release.     

Comparative haemodynamic effects of dobutamine and isoproterenol in man

Dobutamine was infused at a rate of 8 mcg/kg/min in 17 patients with or without congestive heart failure. Cardiac output increased from an average 2.92 to 4.45 1/min/m2 (p<0.001) with no change in mean aortic pressure (93.4 to 97.8 mmHg) and only a slight increase in heart rate (78 to 87 beats/min). Left ventricular end-diastolic pressure decreased from an average 19 to 13.7 mmHg (p<0.01). Peak left ventricular dp/dt was doubled (1147 to 2370 mmHg/sec, p<0.001) and Vmax increased from 1.08 to 2.18 circ/sec (p<0.001). In 10 patients given equi-inotropic doses (100 per cent increase in peak dp/dt) Isoproterenol produced a greater increase in cardiac output (71 percent) than Dobutamine (51 percent). isoproterenol caused mean aortic pressure to fall significantly (8 percent) while no change was noted with Dobutamine. Accordingly, peripheral vascular resistances were reduced to a greater extent with Isoproterenol than with Dobutamine (p<0.05). Mean pulmonary arterial pressure decreased significantly (25±5.9 to 22±5.7 mmHg, p<0.05) with Isoproterenol infusion and remained unchanged with Dobutamine infusion. Dobutamine increased both stroke work (57 percent) and minute work (83 percent). With Isoproterenol however, only minute work was significantly increased (90 percent). Dobutamine therefore is a potent inotropic drug, with mild chronotropic and peripheral vascular effects and may be valuable in the management of severe heart failure not associated with hypotension.     

Sar1-Ala8 angiotensin II blocks renin-angiotensin but not beta-adrenergic dipsogenesis

Continuous, intravenous (IV) infusion (10 μg/min) of Sar¹-Ala⁸ angiotensin II (P-113), an angiotensin II blocking analog, into rats greatly attenuated water intake resulting from IV renin (4 U) and IV angiotensin II (80 μg). P-113 infusion did not attenuate the drinking induced by the subcutaneous (SC) administration of beta-adrenergic agents: isoproterenol (0.05 mg/kg), quinterenol (4 mg/kg), and diazoxide (40 mg/kg). P-113 also functioned as a weak agonist with respect to the drinking response. It was concluded that beta-adrenergic dipsogenesis in not attributable to renin release but does depend upon some unknown renal endocrine factor.     

alpha- and beta-receptor blockade of isoproterenol- and norepinephrine-induced effects on regional blood flow and blood flow acceleration.

The effects of the beta-receptor blocking agent propranolol (100 microgram/kg i.v.) and of the alpha-receptor blocking agent dihydroergotamine (50 microgram/kg i.v.) on hemodynamic responses to isoproterenol and norepinephrine (both 1--1024 ng/kg) were investigated in anesthetized dogs. The effects studied were: (1) flow in the ascending aorta and the coronary, common hepatic, gastroduodenal, splenic, cranial mesenteric, renal and femoral arteries: (2) maximal flow acceleration in the splenic, cranial mesenteric and femoral arteries; (3) maximal rate of change of left ventricular pressure (LV dP/dt max). Propranolol shifted the dose-response curves for the isoproterenol-induced flow increases in the common hepatic, gastro-duodenal, and cranial mesenteric arteries to the right. It did not influence the flow responses to isoproterenol in the ascending aorta or the coronary, splenic, renal and femoral arteries. Propranolol prevented the decrease of arterial pressure evoked by isoproterenol. Propranolol shifted the isoproterenol-induced increase of LV dP/dt max and maximal blood flow to the same extent. Propranolol blocked the flow to the liver and gastrointestinal tract to a greater extent than the LV dP/dt max and maximal flow acceleration. Propranolol had no effect on the norepinephrine-induced increases in flow in the splenic, femoral and coronary arteries, but blocked the norepinephrine-evoked increases of flow accelerations and LV dP/dt max to the same extent. Dihydroergotamine inhibited the norepinephrine-induced increase in flow in the femoral artery and the decreases in flow in the hepatic, splenic, cranial mesenteric and renal arteries, and reversed the reduction of flow in the gastroduodenal artery. It is argued that dihydroergotamine may inhibit the increase in femoral flow through two mechanisms: (1) blocking the flow reduction to norepinephrine in the abdomen, and thereby passively shunting blood from the abdomen in preference to the femoral bed; (2) attenuating the norepinephrine-evoked reflexogenic femoral vasodilatation. It is concluded that: (1) propranolol is a beta-receptor blocking agent with a preference for blockade of isoproterenol-induced vascular effects; (2) norepinephrine-induced flow increases are not direct actions on vascular beta-receptors; (3) the increase of maximal blood flow accelerations after isoproterenol and norepinephrine is mediated by stimulation of cardiac beta-receptors; (4) dihydroergotamine is an alpha-receptor blocking agent particularly in the splanchnic vascular region.     

The effects of apomorphine and isoproterenol on the ‘transport response’ in the white rat

In a series of four experiments, the ability of specific catecholaminergic agonists to intensify the ‘transport response’ was investigated in 19-, 32-, 36- and 40-day-old rats. The dopaminergic agonist, apomorphine, was able to intensify the response in a dose-dependent fashion. The beta-noradrenergic agonist, isoproterenol, was unable to alter the intensity of the response. These results indicate a central dopaminergic involvement in the transport response.     

Chronic beta-adrenoceptor stimulation and cardiac hypertrophy with no induction of circulating renin

The hemodynamic and cardiac effects of isoproterenol were examined in rats submitted to chronic salt loading (1% NaCl as drinking water) to prevent activation of the systemic renin–angiotensin system. Isoproterenol treatment for 1 week resulted in 36% and 44% (P < 0.05) increase in left ventricle mass in both control and chronic salt loading rats and induction of cardiac angiotensin-converting enzyme activity and expression (P < 0.05) with no changes in serum angiotensin-converting enzyme. Plasma renin activity decreased significantly with chronic salt loading and failed to increase by isoproterenol treatment, whereas it increased 2.33 fold (P < 0.05) in animals kept on regular chow. Isoproterenol treatment leads to transient increase in heart rate and cardiac output while blood pressure remained unchanged. Altogether, these data provide evidence that isoproterenol induced hypertrophy is associated with cardiac induction of angiotensin-converting enzyme and daily transient hemodynamic overload even in the absence of systemic activation of renin–angiotensin system.