摘要:

SUMMARY1. The effects of amiloride (M, 20 mg/day), chlorothiazide (C, 1000 mg/day), ethacrynic acid (E, 100 mg/day) and frusemide (F, furosemide 80 mg/day), given alone and in combination, were investigated in eight patients in a 24factorial study. Effects between blocks of four treatments in each sixteen‐treatment replicate were confounded with higher interactions to allow for differences between early and late diuresis.2. All patients exhibited marked diuresis, with significant mean increases in daily urinary sodium excretion (P<0·05) and urinary volume (P<0·01) induced by chlorothiazide, frusemide and ethacrynic acid (68, 69 and 38%; and 35, 40 and 34%, respectively). Amiloride appeared to be half to one‐third as potent as the other diuretics.3. Amiloride produced a significant potassium‐sparing effect (P<0·01), reducing urinary potassium excretion by 30%, compared to significant urinary potassium wasting with frusemide (increase of 33%,P<0·01) and chlorothiazide (increase of 31%,P<0·05).4. No adverse reactions occurred, but serum potassium levels twice rose to 6 mmol/l and subsided without additional therapy, and on one occasion fell to 2·5 mmol/l, requiring a potassium supplement for 4 days.5. It was concluded from these factorial studies that amiloride is a mild diuretic and potent potassium‐sparing agent acting independently and additively in combination with chlorothiazide, ethacrynic acid or frusemide. For the three latter diuretics, all two‐drug interactions were simply additive also, without evidence of synergism or antagonis

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01834.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Plasma renin concentration (PRC) and blood pressure were studied sequentially, 24 h to 42 days post‐operatively, in rats subjected to unilateral renal artery constriction without contralateral nephrectomy.2. The PRC of rats failing to develop hypertension remained normal, whereas the mean PRC of twenty‐two rats that became hypertensive was five times normal on day 14 of the study when the hypertension was becoming established.3. In eleven of the twenty‐two rats that became hypertensive, PRC did not exceed the upper limit of normal. In the remaining hypertensive rats, the increase in PRC was not always temporally related to the increase in blood pressure. A significant correlation between PRC and blood pressure did not emerge until day 35 of the study4. Despite these anomalies, linear regression analysis of 169 pairs of PRC and blood pressure measurements during the 42 day period of development of hypertension in twenty‐two rats revealed a highly significant correlation between log PRC and blood pressure (P<0·001).5. It is concluded that factors other than the plasma concentration of renin are involved in the early stages of development of hypertension induced by renal artery constriction. Nevertheless, PRC and blood pressure are intricately

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01835.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The cardiovascular effects of prazosin, a new antihypertensive drug, were studied in normotensive and genetically hypertensive rats.2. Prazosin, infused intra‐arterially, lowered vascular resistance in the blood‐perfused rat hind limb. This effect was dependent on the presence of intact sympathetic innervation to the limb; no direct vasodilatation was demonstrated. In this preparation prazosin infusion reduced vasoconstrictor responses to nor‐adrenaline.3. In the saline‐perfused rat mesenteric artery preparation prazosin reduced responses to noradrenaline and sympathetic nerve stimulation but not those to serotonin and vasopressin. Prazosin was more potent than phentolamine, on a molar basis, in reducing the vasoconstrictor effects of noradrenaline.4. A comparison of the effects of prazosin injected intravenously and into a lateral cerebral ventricle failed to show any central action of the drug on blood pressure. Experiments using the donor blood‐perfused, vascularly isolated rat hind limb preparation confirmed that the sympatholytic effect of prazosin occurred within the li

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01836.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Calcium did not influence the spontaneous release of vasopressin from rat neurohypophysesin vitrowhen used in concentrations of 0·05, 0·5 and 2·8 mM in the bathing medium.2. Stimulation of the basal output of vasopressin by angiotensin II (1 · 10–9M) required at least 0·5 mM calcium in the medium.3. Angiotensin II stimulated the release of vasopressin within 2·5 min of incubation, maximal release was observed after 10 min.4. Angiotensin II rapidly promoted the accumulation of tissue cyclic AMP; maximal accumulation was observed after 5 min of incubation.5. Theophylline and dibutyryl cyclic AMP produced varying degree of stimulation of the release of vasopressin.6. Increases in vasopressin secretion and in the accumulation of cyclic AMP were always present when neurohypophyses were exposed to optimal concentrations of angiotensin II. The results presented suggested that cyclic AMP may be an intermediate step for the release of vasopressin by endogenous angiote

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01837.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Angiotensin I, a decapeptide, stimulated the accumulation of cyclic 3',5'‐AMP (cyclic AMP) and the release of vasopressin from incubated rat neurohypophyses.2. Various octapeptides related to angiotensin II were capable of producing similar neurohypophyseal effects.3. Longer incubation periods were needed with peptides having alterations or omission (e.g. heptapeptide 2–8) at position 1 of the parent molecule to evoke similar effects to those of angiotensin II.4. Our results suggest strongly that physiological doses of angiotensin‐related molecules stimulate the secretion of vasopressin through cyclic AMP, and that the neurohypophyseal receptor responsible for these effects is similar to that involved in their peripheral ac

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01838.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The acute malignant phase of hypertension in rats with an untouched contralateral kidney is characterized by salt and fluid loss, increased fluid intake, decrease in body‐weight gain, and reduced food consumption. Plasma concentrations of sodium and potassium were reduced, and plasma angiotensin II rose to about four times normal.2. To investigate the significance of an untouched contralateral kidney for the development of the acute malignant phase in renal hypertensive rats, comparative studies were undertaken in unilaterally nephrectomized rats with stenosis of the remaining renal artery and in rats with bilateral renal artery stenosis. In addition, the effect of declamping one renal artery in rats with bilateral stenosis was studied.3. In unilaterally nephrectomized rats, no signs of sodium and fluid loss were demonstrable, despite marked increase in blood pressure. Similarly, rats with bilateral renal artery stenosis had no acute malignant phase of hypertension.4. In hypertensive rats with bilateral stenosis, removal of the clip from one renal artery was followed by an immediate fall in blood pressure and a subsequent gradual increase. Eleven of sixteen rats lost salt and fluid and developed an acute malignant phase. Plasma angiotensin II was high and serum urea elevated.5. Consumption of 2% saline in addition to water as drinking fluid had a beneficial effect, since only five of fourteen rats showed signs of the acute malignant phase, which were milder than in rats on water only.6. It is concluded that the untouched contralateral kidney is responsible for the negative salt and water balance and its consequences, which are characteristic of the acute malignant phase of experimental renal hypertensio

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01839.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Driven left atrial preparations were used to study inotropic responses to isoprenaline and tolbutamide.2. Decreasing the external calcium concentration from 2·2 to 1·1 and 0·55 mM decreased resting force of contraction but increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50values.3. Decreasing the external calcium concentration from 2·2 to 1·1 mM also increased the maximal inotropic responses to tolbutamide. These responses were 23‐and 44‐fold less than those to isoprenaline at equivalent calcium concentrations.4. Preparations maintained in 1·1 mM calcium were used to compare inotropic responses to isoprenaline and tolbutamide at different frequencies of stimulation.5. Decreasing the frequency of stimulation from 4 to 2 or 1 Hz decreased the resting force of contraction and increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50values.6. No significant inotropic responses to tolbutamide were observed at 4 Hz. Positive inotropic responses of similar magnitude occurred at 2 and 1 Hz. The maximal inotropic responses at these frequencies were 43‐and 127‐fold less than those to isoprenaline.7. It is concluded that tolbutamide is a very weak in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01840.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The rate of clearance of125I‐labelled porcine neurophysins I and II from the circulation of the rat has an initial fast component followed by a slower component.2. In the initial phase of clearance the half‐life of neurophysin I was 1·50 min (s.e.m. = 0%%03) and for neurophysin II was 1·74 min (s.e.m. = 0·05). In the slower phase of clearance the half‐life of neurophysin I was 22·6 min (s.e.m. = 2·2) and for neurophysin II was 27·3 min (s.e.m. = 5·8).3. The first component had a volume of distribution similar to the blood volume and the second component had a volume of distribution similar to the volume of extracellular fluid of the rat.4. The metabolic clearance rates per 200 g of body weight were 1·94 ml/min (s.e.m. = 0·12) for neurophysin I and 1·29 ml/min (s.e.m. = 0·15) for neurophysin II.5. Using whole‐body autoradiography, the kidney was shown to be the major site of uptake of radioactivity in both virgin female

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01841.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Prostaglandin E1(0·4 mg/kg, i.p.) significantly potentiated the antinociceptive action of morphine in albino rats.2. This potentiation was significantly inhibited by pretreatment with reserpine,p‐chlorophenylalanine or methysergide but not by α‐methyl‐p‐yrosine, phentolamine or propranolol.3. The results suggest that the potentiation of morphine by prostaglandin E1is mediated by serotonin, since it is inhibited by pharmacological agents known to reduce central turnover of serotonin

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01842.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Three 3‐methanesulphonamido, 4‐hydroxy ring substituted phenylethanol‐amines withn‐isopropyl (soterenol),n‐t‐butyl (MJ7999–1) andn‐(1‐phenyl‐t‐butyl) (MJ9184–1) amine substituents have been compared with (—)‐isoprenaline for their ability to produce β‐receptor mediated reductions in serotonin‐induced increases in pulmonary resistance, decreases in soleus muscle contractility, and increases in heart rate in anaesthetized cats. For each parameter, the dose of a compound required to produce 50% of its maximal response (ED50) was calculated.2. For all three parameters (—)‐isoprenaline was the most potent of the compounds studied, and the rank order of potency of the methanesulphonanilides was MJ9184–1 (n‐(1‐phenyl‐t‐butyl))≃MJ7999–1 (n‐t‐butyl)>soterenol (N‐isopropyl).3. For each individual drug, molar dose‐ratios [drug: (—)‐isoprenaline] were calculated. Ratios for the effects of the compounds on the soleus muscle and in the bronchi were similar. With each compound higher dose‐ratios were found in the heart. The rank order for relative β2‐selectivity was soterenol

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01843.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY