EFFECTS OF ATRIAL NATRIURETIC PEPTIDE ON PHENYLEPHRINE-INDUCED RENIN RELEASE IN DOGS

1. The effect of atrial natriuretic peptide (ANP) on alpha-adrenoceptor agonist-induced renin release was examined in the de-ennervated kidney of the anaesthetized dog pretreated with propranolol (1 mg/kg, intravenous). 2. Phenylephrine (50 ng/kg per min) infused into the renal artery increased the renal secretion rate of renin (RSR) without affecting systemic blood pressure or renal blood flow. 3. Although basal RSR was unaffected, the phenylephrine-induced increase in RSR was abolished during intrarenal arterial infusion of ANP (10 ng/kg per min). 4. The results suggests that exogenously administered ANP could suppress alpha-adrenoceptor-mediated renin release in the dog.     

EFFECTS OF PROSTACYCLIN AND PROSTAGLANDIN E2 ON THE SECRETION OF PANCREATIC JUICE IN THE DOG

1.Effects of prostacyclin (PGI₂) and prostaglandin E₂ (PGE₂) on the secretion of pancreatic juice were investigated in preparations of the blood-perfused canine pancreas. 3 These results suggest that PGE₂, but not PGI₂, may control the secretory mechanism of the pancreatic secretion in dogs.     

EFFECT OF PROSTAGLANDIN E2 ON SERUM IRON AFTER ACUTE AND CHRONIC BLOOD LOSS

The effect of prostaglandin E2 on serum iron of New Zealand rabbits subjected to acute and chronic blood loss is demonstrated. The results showed that acute blood loss was followed by significant elevation of serum iron when sera were tested on day three after the bleeding. With subcutaneous injection of 40 micrograms/kg body weight of prostaglandin E2 for each 12 h of the experiment, acute blood loss was followed by a significant reduction in serum iron within the same period. Similar results were obtained after chronic blood loss when subcutaneous injection of 20 micrograms/kg body weight of prostaglandin E2 was used for each 12 h of the experiment. It could be concluded that the prostaglandin E2 causes marked lowering of serum iron following blood loss.     

THROMBOXANE B2 INHIBITS PROSTAGLANDIN E2 INACTIVATION BY THE RAT ISOLATED PERFUSED LUNG

1. The effect of thromboxane B₂ (T×B₂) on inactivation of prostaglandin E₂ (PGE₂) by the rat isolated perfused lung has been studied. 2. TxB₂ when infused in low concentrations (100 ng/ml) into the pulmonary artery reduced PGE₂ inactivation approximately two-fold. 3. The rat isolated fundus strip was contracted by higher concentrations of TxB₂ (1.0 Mg/ml) in the presence of hyoscine, mepyramine, methysergide, phenoxy-benzamine and propranolol. The size of contraction was reduced by indomethacin in concentrations known to inhibit prostaglandin synthetase. 4. Thus, in circumstances in which T×B₂ and PGE₂ are released concomitantly by the lung, low concentrations of TxB₂ may augment PGE₂ release by reducing its inactivation.     

EFFECTS OF PROSTAGLANDIN D2 AND OMEPRAZOLE ON INDOMETHACIN-INDUCED GASTRIC ULCERS IN RATS

1. The mechanism of indomethacin-induced gastric ulcers was investigated by measuring tissue prostaglandins (PG) levels. 2. The effects of PGD2 and omeprazole, an H+ pump inhibitor, were also estimated. 3. Four kinds of PG--6-keto PGF1 alpha, PGF2 alpha, and PGD2--in rat gastric mucosa were measured by high performance liquid chromatography. 4. All PG levels decreased 1 h after oral administration of 2 mg/kg indomethacin, although they recovered considerably 24 h after administration. No gastric ulcers were observed throughout the experiments in rats treated with 2 mg/kg indomethacin. 5. All PG were not detected 1 h, and even 24 h after administration of 12 mg/kg indomethacin. Over 6 h after administration, gastric ulcers were observed. 6. Premedication with omeprazole prevented ulcer formation, although it did not improve gastric mucosal PG levels. Administration of PGD2 also reduced ulcer formation, and considerable amounts of PGD2 in gastric mucosa were detected. 7. It can be concluded that H+ is a determining factor in the genesis of indomethacin-induced gastric ulcers and that persistent decreases in tissue PG levels also participate in ulcer formation.     

INTRACORONARY PGE2 AND VERATRINE INHIBITS RENIN RELEASE IN CONSCIOUS DOGS VIA CHEMOSENSITIVE VENTRICULAR AFFERENTS

1. Prostaglandins (PG) and veratrum alkaloids stimulate ventricular sensory receptors with non-myelinated vagal afferents and mediate inhibitory circulatory responses. 2. The present study in conscious instrumented dogs was carried out to determine the effects of intracoronary artery infusions of veratrine (Ver-IC) and PGE2 (PGE2-IC) on plasma renin activity (PRA). 3. A 15-20 mmHg decrease in arterial pressure was produced during Ver-IC (0.2-0.8 micrograms/kg per min) and PGE2-IC (10-50 ng/kg per min), but there was no change in PRA or heart rate. 4. In contrast, significant increases in PRA (+3.51 +/- 0.37 ng angiotensin I/mL per h; P less than 0.01) and heart rate (+38.5 +/- 6.2 beats/min; P less than 0.001) were elicited in response to a 15-20 mmHg decrease in arterial pressure produced by intravenous infusions of nitroprusside. 5. Pharmacological blockade of afferent fibres in the pericoronary region of the left main coronary artery during Ver-IC resulted in significant hypotension-induced increases in PRA (P less than 0.001) and heart rate (P less than 0.001), thus removing the inhibitory influence of chemosensitive ventricular afferents. 6. Therefore, intracoronary veratrum alkaloids and prostaglandins inhibit hypotension-induced increases in PRA and heart rate in the conscious dog. This is mediated by chemosensitive receptors located in the left ventricular myocardium along with afferent nerves in the pericoronary region and cervical vagi.     

EFFECTS OF PROSTAGLANDIN E2 ON RENAL FUNCTION AND LUNG LIQUID DYNAMICS IN FOETAL SHEEP

1. The aim of the present study was to determine the effects of prolonged prostaglandin E₂ (PGE₂) administration on the function of the foetal kidneys and lungs in order to gain a greater understanding of the role played by PGE₂ in the control of foetal fluid balance. By studying the effects of PGE2 at two gestational ages, we have also been able to examine the influence of age. 2. We studied the effects of 26 h PGE2 infusion on foetal sheep at a mean (±SEM) of 120.0 ± 0.6 (n= 6) and 139.0 ± 0.8 (n= 4) days of gestation. In both groups, foetal urine production was significantly inhibited throughout the infusion period (P < 0.05). In younger, but not older foetuses, urine production returned to control values within 24 h of ending the infusion (P < 0.05). This PGE2-induced anti-diuresis was associated with foetal hypoxaemia and acidaemia, a reduction in free water clearance and an increase in foetal plasma arginine vasopressin concentrations (P < 0.05). 3. During PGE₂ infusions, foetal breathing movements were inhibited, the effect being greater and more sustained in older foetuses (P < 0.05). 4. Infusions of PGE₂ led to increased lung liquid production at both ages (P < 0.05); lung liquid volumes were reduced in older foetuses (P < 0.05), but were unchanged in younger foetuses. The reduction in lung liquid volume in older foetuses may have been due to inhibition of foetal breathing. 5. We conclude that increased circulating levels of PGE2 have profound effects on foetal renal and lung function which, if sustained, could compromise foetal lung development and perinatal well-being.     

PROSTAGLANDINS: ANTINOCICEPTIVE EFFECT OF PROSTAGLANDIN E1 IN THE RAT

1. The antinociceptive effect of prostaglandins E₁, E₂ and F_2α was studied in albino rats. Though all three prostaglandins produced similar degrees of sedation, only prostaglandin E₁ (PGE₁) produced a dose-related antinociceptive activity. 2. The antinociceptive activities of equi-analgesic doses of morphine (7.5 mg/kg, i.p.) and PGE₁ (2.0 mg/kg, i.p.) were inhibited to almost similar extents after pretreatment with drugs known to reduce central turnover of serotonin receptors, namely reserpine, fenclonine (p-chlorophenylalanine), methysergide and 5,6-dihydroxytryptamine. 3. Prostaglandin F_2α (2.0 mg/kg, i.p.) significantly inhibited the antinociceptive effects of both morphine and PGE₁. 4. The prostaglandin synthesis inhibitors, indomethacin and diclofenac, significantly inhibited morphine analgesia. 5. Probenecid markedly prolonged the duration of antinociceptive effect of morphine and the duration of PGE₁-induced potentiation of subanalgesic dose of morphine. 6. The results suggest that, in albino rats, PGE₁-induced antinociceptive activity is serotonin mediated and that morphine analgesia is not only mediated through serotonin but also through prostaglandins (PGE₁?) and 5-hydroxyindole acetic acid, the serotonin metabolite.     

6-KETO-PROSTAGLANDIN E1 AND PROSTAGLANDIN E2 STIMULATE ALDOSTERONE PRODUCTION IN BOVINE ADRENAL GLANDS

In order to investigate the effect of prostaglandins on aldosterone synthesis, dispersed bovine adrenal cells were incubated with prostaglandins and the aldosterone concentration was measured by radioimmunoassay. The result was that aldosterone production was stimulated by 6-keto-prostaglandin E1 and prostaglandin E2.     

IN VIVO AND IN VITRO EFFECTS OF ATRIAL NATRIURETIC PEPTIDE ON RENIN RELEASE

1. This study investigated the effect of atrial natriuretic peptide on renin release from the kidney. The in vitro direct effect was examined in the animal experiment using renal cortical slices of rat, and the in vivo effect was observed in the human infusion study. 2. In the in vitro experiments, alpha-human atrial natriuretic peptide (alpha-hANP) ranging 10(-9) to 10(-6) mol/L did not change the basal renin release rate from the renal cortical slices (-9% at 10(-6) mol/L, NS). Isoproterenol (10(-6) mol/L) increased renin release by 40% (P < 0.001), whereas angiotensin II (10(-6) mol/L) suppressed it by 48% (P < 0.001). However, alpha-hANP did not affect the stimulative effect of isoproterenol or the inhibitory effect of angiotensin II. 3. Also in the human study, infusion of 25 ng/kg per min alpha-hANP failed to change the plasma renin activity in normotensive subjects (-4%) or patients with essential hypertension (+5%), or even in patients with raised renin levels such as renovascular hypertension (+10%) or congestive heart failure (-13%). 4. These results put forth negative views on the direct involvement of atrial natriuretic peptide in renin release from the juxtaglomerular apparatus.     

PROSTAGLANDINS DO NOT MEDIATE RENIN RELEASE DURING SEVERE REDUCTION OF RENAL BLOOD FLOW IN CONSCIOUS DOGS

1. Renal blood flow was reduced by about 80% for 90 min in chronically instrumented conscious dogs following aspirin, indomethacin or no pretreatment. 2. There were no significant differences between the rises in plasma renin activity in the three groups of dogs (+ 7.9, s.e.m. = 1.4; +8.1, s.e.m. = 1.5; and +7.5, s.e.m. = 1.8 ng/ml per h, respectively) or in mean arterial pressure (36.0, s.e.m. = 5.6; 38.6, s.e.m. =2.6, or 35.4, s.e.m. =4.7 mmHg; respectively). 3. These results strongly suggest that prostaglandins do not mediate renin release during severe reduction of renal blood flow in conscious dogs.     

THE EFFECT OF PHENTOLAMINE ON ACTIVE AND INACTIVE RENIN RELEASE IN HUMAN RENOVASCULAR HYPERTENSION

1. Phentolamine was infused at low increasing doses (0.2, 0.3, 0.4 and 0.5 mg/min) in five patients with unilateral renal artery stenosis measuring active and inactive (cryoactivable) renin in the renal veins from the stenosed and nonstenosed kidney and in a peripheral vein. 2. PRA values from the stenosed kidney (11.59, s.e.m. = 5.79 pmol ang I/ml per h) were higher than those in the peripheral vein (5.19, s.e.m. =2.64) while these latter were similar to those from the contralateral kidney (5.09, s.e.m. =2.93). Phentolamine significantly increased PRA from the stenosed kidney and in the peripheral vein in a dose-related manner. PRA changes were unrelated both to blood pressure decrements and to heart rate increments induced by the drug. 3. Before phentolamine, inactive renin from the stenosed kidney (5.19, s.e.m. = 2.84 pmol ang I/ml per h) did not differ significantly from that on the contralateral side (3.15, s.e.m. = 1.96) and in the peripheral vein (4.40, s.e.m. = 1.96). Phentolamine induced significant (P < 0.005) increments of inactive renin only from the stenosed kidney at the doses of 0.3, 0.4 and 0.5 mg/min. Inactive renin from the contralateral kidney was unchanged and it tended to increase, but not to a significant extent, in the peripheral vein. A highly significant relationship was found between active and inactive renin from the stenosed kidney (r = 0.79, P < 0.001, n= 25) and in peripheral blood (r = 0.71, P < 0.001, n= 25) but not from the stenosed kidney (r = 0.29, n= 25). 4. These results suggest that phentolamine, infused at low increasing doses causes an increase of PRA only in the stenosed kidney, an action which does not seem to be wholly explained by either sympathetic nervous system activation or decrease of renal perfusion pressure, and which suggests an action on intrarenal a-adrenoreceptors. Furthermore, phentolamine stimulated inactive renin release only from the stenosed kidney without evidence of intrarenal conversion of the inactive into the active form.     

EFFECT OF MINERALOCORTICOIDS AND SALT LOADING ON RENIN RELEASE, RENAL RENIN CONTENT AND RENAL RENIN mRNA IN MICE

1. DOCA and 9 alpha-fludrocortisone were given to mice on a high-sodium diet for periods of up to 20 weeks, resulting in decreases in plasma renin concentration, renal renin concentration and renal renin mRNA with both treatments. 2. Plasma renin concentration was suppressed prior to suppression of renin mRNA and renal renin levels, indicating that suppression of synthesis and secretion of renin occur separately. 3. The decrease in renal renin concentration that occurred with DOCA was greater and more rapid than the decrease that occurred with 9 alpha-fludrocortisone, suggesting that DOCA caused intra-renal breakdown of renin. 4. When DOCA was given to mice on a low-sodium diet, plasma renin concentration and renal renin concentration increased, indicating that the effects of DOCA on renin levels were dependent on dietary sodium. 5. Renin secretion and synthesis appeared to be controlled by different mechanisms and sodium balance has an important effect on both processes.     

尼索地平对麻醉犬心肌耗氧量和血流动力学的影响

尼索地平(2,5,10μ/kg iv)能降低麻醉犬心肌耗氧量8.23％、26.9％和34.1％。它能明显降低收缩压(SBP)、舒张压(DBP)及总外周阻力(TPR),增加冠脉流量(CBF)、心输出量(CO);对左室收缩压(LVSP)、压力上升速率最大值(±dp/dtmax)和心率(HR)无明显影响。而参比药物硝苯啶20μg/kgiv虽能降低心肌耗氧量,但其效果明显低于尼索地平的3个剂量组。而且,硝苯啶使实验犬心脏的LVSP和-dp/dtmx均有显著降低。表明本品与硝苯啶不同,对心肌本身并无作用。     

EFFECTS OF NEUROPEPTIDE Y ON THE PRESSOR RESPONSES TO PHENYLEPHRINE AND TO ACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM IN ANAESTHETIZED RATS

1. The effects of neuropeptide Y (NPY) on the pressor responses to intravenous injections of phenylephrine and to reflex activation of the sympathetic nervous system by stimulation of the sciatic nerve were examined in anaesthetized rats. 2. NPY (10-20 micrograms/kg) always potentiated the pressor response to exogenous phenylephrine (by a mean of 28.1 +/- 5.0%). The effect of the same dose of NPY on the pressor response to sciatic nerve stimulation was variable (sometimes inhibition, sometimes potentiation). 3. NPY appears to act by potentiating post-synaptic alpha-adrenoceptor-mediated vasoconstrictor effects. It may also inhibit noradrenaline release by a presynaptic action. Thus the net effect of NPY on sympathetic activation in vivo may depend on the balance between these two opposing actions.     

EFFECTS OF TORASEMIDE ON RENAL HAEMODYNAMICS AND FUNCTION IN ANAESTHETIZED DOGS

1. We examined the effects of torasemide (0.3 and 1 mg/kg i.v.) on renal haemodynamics and function employing renal clearance and stop-flow techniques in anaesthetized dogs and compared these with furosemide (1 and 3 mg/kg i.v.). 2. Torasemide and furosemide did not influence renal haemodynamics, in the renal clearance study, but caused a dose-related and significant increase in urine flow and urinary excretion of sodium and potassium. Torasemide and furosemide increased fractional excretion of sodium in the distal tubules with a relatively small increase in the fractional excretion of lithium (index of sodium excretion at the proximal tubules, FELi). The diuretic profile of torasemide was of long duration, compared with that of furosemide. 3. Torasemide and furosemide inhibited sodium reabsorption at the distal portion of the tubules in the stop-flow study. 4. It is suggested from these results, that the main diuretic site of action of torasemide is the ascending limb of the loop of Henlé.     

CARDIOVASCULAR EFFECTS OF AMITRIPTYLINE IN ANAESTHETIZED DOGS

1. The effect of amitriptyline on cardiovascular variables has been studied in anaesthetized dogs. 2. In small doses (0.25 mg/kg) amitryptyline caused small increases in heart rate, contractility, blood pressure, coronary blood flow and aortic flow. 3. Larger doses produced initial depressant effects on myocardial contractility and rate and blood pressure, which were followed by secondary reflex rises in these measurements. 4. The depressant effects were dose-related and were accompanied by marked increases in coronary flow and smaller increases in aortic flow. 5. The secondary reflex rises in cardiac parameters were abolished by propranolol and that of the blood pressure was much reduced.     

MODULATION OF ADRENAL CATECHOLAMINE RELEASE BY DA2 DOPAMINE RECEPTORS IN THE ANAESTHETIZED DOG

1. The effects of DA2 agonist, quinpirole (50 micrograms/kg, i.v.) and a DA2 antagonist, domperidone (50 micrograms/kg, i.v.) on the release of adrenal catecholamines were evaluated in the anaesthetized and vagotomized dog. 2. Stimulations (5 V pulses of 2 ms duration for 3 min) of the splanchnic nerve at frequencies of 1, 3 and 5 Hz were applied randomly before and after injection of the drug. 3. The results show that quinpirole reduces significantly the release of adrenaline at 1 and 3 Hz but not at 5 Hz, while the release of noradrenaline is reduced at 1 Hz but not at 3 and 5 Hz. Inversely, domperidone potentiates significantly the release of both catecholamines at 3 and 5 Hz, but not at 1 Hz. 4. There was no change in basal release of adrenal catecholamines, adrenal blood flow or heart rate after both drug treatments. 5. The mean arterial pressure was not affected by domperidone treatment but there was a significant reduction in basal mean arterial pressure after the injection of quinpirole. 6. There was no change in any of these parameters during electrical stimulation. 7. Therefore, these results strongly suggest that DA2 dopamine receptors are present at the level of the adrenal medulla and that their activation could mediate an inhibitory modulation on the adrenal catecholamines release within a certain range of electrical stimulation.     

苯妥英钠与前列腺素E2联合应用抗实验性哇巴因心律失常的研究

关于联合用药治疗心律失常,目前报道甚少,对此问题深入地进行基础理论或临床治疗学的研究,具有实际意义。已知苯妥英钠(DPH)为治疗洋地黄心律失常的有效药物。近年来亦发现前列腺素E(PGE)有抗哇巴因心律失常的作用,但其机制待深入探讨。一般认为洋地黄心律失常与交感神经活动增强有关,并发现洋地黄致心律失常时心肌儿茶酚胺含量