摘要:

SUMMARY1. This study investigated first the effects of forskolin on cardiac rhythm, and second the roles of calcium in cardiac arrhythmogenesis by cAMP.2. Two series of experiments were performed. In the first series, forskolin was administered into the isolated perfused rat heart. In the second series, forskolin administration was preceded by administration of nifedipine, a calcium channel blocker, or infusion of a low concentration calcium solution. In both experiments, the myocardial cAMP level and electrocardiogram were determined.3. It was found that forskolin increased cAMP level as well as inducing arrhythmia. Pretreatment with nifedipine or a reduction of external calcium, that either maintained or further enhancd the forskolin‐induced increase in the cAMP level, abolished the forskolin‐induced arrhythmia.4. The results of the present study support the hypothesis that myocardial cAMP mediates cardiac arrhythmia, and provide evidence that calcium is essential in arrhythmia mediated by c

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01513.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. Previous studies demonstrated that the combined infusion of cortisol (F), aldosterone (ALDO), deoxycorticosterone (DOC), corticosterone (B), 11‐deoxycortisol (S), 17α‐hydroxyprogesterone (17αOHP) and 17α, 20α‐dihydroxy‐4‐pregnane‐3‐one (17α20αOHP), at rates equivalent to their production during adrenocorticotrophic hormone (ACTH) treatment, reproduced the pressor and metabolic responses to ACTH administration in sheep.2. This study examined which of these adrenocortical steroids were necessary for the initiation of the hypertension produced by these steroids in sheep.3. Infusion of F, ALDO, 17αOHP and 17α20αOHP together, increased MAP by 19 mmHg, similar to both complete steroid cocktail (+25 mmHg) or ACTH administration (+ 21 mmHg). Infusion of F, 17αOHP and 17α20αOHP increased MAP by +7 mmHg. Infusion of ALDO, 17αOHP and 17α20αOHP had no effect on MAP. Thus F and ALDO were essential for the pressor effects of the steroid infusion.4. To determine the role of glucocorticoid activity in the MAP rise, prednisolone, a non‐pressor glucocorticoid, was substituted for cortisol. Combined prednisolone, ALDO, 17αOHP and 17α20αOHP infusion did not raise blood pressure. This suggested that the mineralocorticoid component rather than glucocorticoid component of cortisol's activity was involved in the pressor response.5. Aldosterone (7 μg/h) was substituted for cortisol, giving a total of 10 μg/h aldosterone. High dose ALDO (10 μg/h), 17αOHP and 17α20αOHP infusion raised blood pressure by 18 mmHg. Thus, the essential role of cortisol appeared to be due to its occupancy of mineralocorticoid receptors, rather than glucocorticoid receptors.6. Given that ACTH produces a transient initial increase in aldosterone secretion of up to 10 μg/h, it appears that aldosterone and not cortisol is essential for the pressor effects of ACTH.7. Hypertension resulting from the combined steroid infusion in the sheep appears to be produced by a mechanism which involves a complex interaction between ALDO, F, 17αOHP and 17α20αOHP. Therefore, the putative ‘hypertensinogenic’ receptor may be multivalent with binding sites for F, ALDO and 17α20αOHP, or is a site of single interactive receptors for these steroids and that F exerts its permissive action by occupying the sam

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01514.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The effects of acute unilateral renal denervation were examined in 17 anaesthetized rats. Renal haemodynamic changes were monitored using standard clearance techniques. Lithium clearance was used to assess fractional proximal sodium and water reabsorption.2. Denervation resulted in ipsilateral renal vasodilatation with marked natriuresis and diuresis, a small increase (15%,P<0.05) in glomerular filtration rate (GFR) and a consequent reduction in filtration fraction. Fractional lithium reabsorption decreased (67.3 ± 2.9% to 54.5 ± 4.0%,P<0.01) and absolute proximal reabsorption did not change, indicating impairment of proximal glomerulotubular balance (GTB). No similar changes in haemodynamic or transport parameters were observed in the contralateral, innervated kidney, although vascular resistance increased.3. In 9 experiments following denervation of the left kidney, systemic low dose infusion (10 ng/min) of atrial natriuretic factor (ANF) resulted in a fall in mean arterial blood pressure from 116 ± 3 mmHg to 107 + 3 mmHg (P<0.05). In the denervated kidney ANF increased urine flow rate and sodium excretion to rates above those established following denervation alone. However, in the right kidney, despite the increased filtered load (35%,P<0.01), the natriuretic and diuretic responses to ANF were abolished.4. In the denervated kidney, ANF further reduced the fractional reabsorption of lithium from 53.6 ± 2.3% to 45.6 ± 3.8% (P<0.05). GFR increased by 32% (a total of 49% higher than during pretreatment) but absolute proximal reabsorption (APR) did not change. However, in the right, innervated kidney ANF infusion produced a 35% increase in GFR accompanied by a 53% rise in APR.5. It is concluded that the natriuresis induced by unilateral denervation is due predominantly to impaired proximal GTB. The natriuretic action of ANF was associated with further impairment of proximal GTB, not dependent upon decreasing activity of renal sympathetic nerves, but was abolished when filtration fraction and renal sympathetic tone were elev

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01515.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. There has been interest in the suggestion that enzyme‐inducing drugs, such as anticonvulsants, may produce beneficial changes in lipoprotein levels, in particular a rise in the ratio of high density lipoprotein cholesterol to total cholesterol.2. This controlled study observed the effects of diets of charcoal or oven‐cooked beef on antipyrine clearance (a commonly used measure of drug metabolizing capacity), the apparent oral clearance of phenacetin (a measure of cytochrome P448‐dependent enzyme activity) and blood lipids in 18 healthy volunteers.3. Charcoal‐cooked beef increased antipyrine clearance by an average of 20% (P<0.059) and increased the apparent oral clearance of phenacetin fivefold (P<0.01). In contrast, oven‐cooked beef did not significantly alter either measure of microsomal function. Neither diet had any effects on blood lipids.4. We conclude that the type and degree of enzyme induction achieved by this type of dietary manipulation does not produce beneficial changes in lipoprotein profiles. A previously noted rise in high density lipoprotein cholesterol levels in volunteers fed charcoal‐cooked beef may have been due to the effects of charcoal formed by charring of the beef dur

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01516.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. Transplacental transfer of the anti‐epileptic agent phenytoin (PHT), its phase I metabolite,p‐hydroxy‐phenytoin (p‐OH‐PHT), and its phase II conjugatep‐OH‐PHT‐glucuronide, was studied in term placental lobules perfused single pass in both maternal and fetal circuits.2. Ratios of clearance of PHT,p‐OH‐PHT andp‐OH‐PHT‐glucuronide to clearance of antipyrine were 1.08 ± 0.03, 0.52 ± 0.02 and 0.12 ± 0.01 (mean and s.e.m.), respectively.3. Transfer was positively correlated with lipophilicity as measured by the apparent partition coefficient determined betwe

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01517.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. Diltiazem (10 μmol/L) and verapamil (10 μmol/L) inhibited the hypercontractility induced by 3% halothane and 2 mmol/L caffeine in malignant hyperpyrexia susceptible (MHS) muscle. Diltiazem also inhibited 80 mmol/L KCl contractures.2. Like the skeletal muscle relaxant dantrolene sodium (6 μmol/L), diltiazem not only prevented but reversed the abnormal contractures induced by halothane and caffeine.3. The effect on caffeine contractures of diltiazem and dantrolene in combination was additive.4. The ability of diltiazem and verapamil to inhibit the hypercontractility of MHS muscle suggests that Ca2+influx across the transverse tubular membrane may be important in the aetiology of the malignant hyperpyrexia syndrome.5. These results also suggest an abnormality in transverse tubule—sarcoplasmic reticulum communica

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01518.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The renal response to renal arterial infusion of synthetic atrial natriuretic factor (ANF 99–126) was examined in conscious sheep following dietary K loading, and compared with the response in normal sheep.2. Renal arterial infusion of ANF in K loaded sheep increased the excretion of Na and Ca, but did not affect the excretion of K.3. The natriuretic effect of ANF was attenuated in K loaded animals, possibly as a consequence of the reduction in Na status which is associated with K loadin

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01519.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY