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At least 757 records · Page 42Linked to original sources
PubMed1993

Renin release induced by losartan (DuP 753), an angiotensin II receptor antagonist.

The AT2 angiotensin receptor antagonist, PD123177, did not elicit plasma renin activity (PRA) or blood pressure effects in conscious unrestrained normal rats at a dose of 30 mg/kg iv. In contrast, losartan (DuP 753), a nonpeptide AT1 angiotensin receptor antagonist, elicited dose-dependent increases in PRA. PRA increased between five- and fifty-fold after intravenous administration of 1-10 mg/kg in the absence of changes in blood pressure. At 3 mg/kg iv, losartan induced a twenty-fold increase of PRA which was of renal origin inasmuch as bilateral nephrectomy blocked the effect. Cyclooxygenase blockade with indomethacin or meclofenamate did not alter losartan-induced renin release at 3 mg/kg iv and suggested that the hyperreninemia was not mediated by renal prostaglandins. The nonselective beta-blocker propranolol and the beta 1 selective blocker atenolol attenuated losartan-induced renin release approximately 70 and 80% respectively without altering blood pressure. These results were consistent with a modulation of renin release by sympathetic nerve activity via beta-adrenergic receptors. The findings suggest that losartan interferes with the ability of angiotensin II to suppress that renin release which is mediated by sympathetic nerve activity.

Angiotensin Receptor Antagonists↗
PubMed1983

Amrinone dilates pulmonary vessels and blunts hypoxic vasoconstriction in isolated rat lungs.

The direct effects of the cardiotonic agent amrinone (WIN 40680) on pulmonary vasoreactivity were studied in isolated, blood-perfused, rat lungs. Lungs were perfused at constant flow and ventilated with normoxic gas, while mean pulmonary arterial pressure was monitored. Pressor responses to hypoxic gas (3% O2, 5% CO2) and angiotensin II (0.25 microgram/0.1 ml) were elicited after amrinone or saline was added to the perfusate. Pressor responses were blunted when calculated amrinone perfusate concentration was increased to 10 micrograms/ml. Pressor responses to hypoxia fell from 8 +/- 1 mm Hg (mean +/- SE, n = 8) before, to 2 +/- 1 mm Hg after amrinone (10 micrograms/ml), while responses to angiotensin II fell from 7 +/- 1 to 3 +/- 1 mm Hg (n = 8). Pressor responses in saline controls did not change. Pulmonary arterial pressure dropped within minutes following injection of amrinone (300 micrograms) into the pulmonary arterial cannula, with a greater drop during hypoxia than during normoxia. Meclofenamate did not prevent blunting of pressor responses by amrinone. Amrinone is a rapidly acting vasodilator which blunts vasoconstriction due to hypoxia or angiotensin II. Since it combines cardiotonic and pulmonary vasodilator actions, amrinone may have therapeutic potential for patients with cor pulmonale and pulmonary hypertension.

Aminopyridines↗
PubMed1985

Prostaglandin modulation of the vascular effects of vasopressin in the conscious rat.

Experiments were performed on conscious, male Sprague-Dawley rats to determine whether cyclooxygenase inhibition affects the pressor response to exogenous vasopressin. The rise in arterial blood pressure was tested in response to 1.0, 2.5, 5.0, and 12.5 mU synthetic arginine vasopressin both before and following cyclooxygenase inhibition with either meclofenamate or the structurally dissimilar inhibitor ibuprofen. In addition, time control experiments were also performed where only the saline vehicle for the drugs was administered. In all animals tested, the increase in arterial pressure in response to the highest three concentrations of vasopressin was greater following cyclooxygenase inhibition than before, while the saline vehicle had no effect. The baroreceptor-mediated bradycardia accompanying the rise in blood pressure was variable, but unaffected by meclofenamate or ibuprofen. It is concluded that vasodilator prostaglandins are released in response to pressor levels of vasopressin, which act to modulate the pressor response of the peptide.

Animals↗
PubMed1986

Prostaglandins modulate baroreflex-induced changes in blood pressure and myocardial function in anesthetized dogs.

The purpose of our study was to investigate the role of prostaglandins in the changes in myocardial function and peripheral and coronary vascular resistance which accompany a generalized increase in sympathetic tone caused by carotid baroreflex unloading in the anesthetized dog. Bilateral carotid artery occlusion (BCO) with heart rate held constant by electrical pacing (150 beats/min) resulted in increases in systolic, (33%) diastolic (40%), and mean (35%) arterial pressures, LV systolic pressure (33%) and left ventricular (LV) dP/dt (37%). After blockade of prostaglandin synthesis with indomethacin (N = 11) or meclofenamate (N = 6) the increases in systolic (41%), diastolic (45%), and mean (41%) arterial pressures, LV systolic pressure (39%), LV dP/dt (52%), and cardiac work caused by BCO were significantly greater, in spite of the initially higher baseline values (11-18%) following the administration of the drugs. In contrast, the changes in circumflex coronary blood flow and coronary vascular resistance to BCO were essentially the same before and after inhibition of prostaglandin synthesis. Systemic prostaglandin synthesis may, therefore, play a significant role in the control of systemic arterial pressure and myocardial function, most probably by modulating the release of norepinephrine from adrenergic nerve terminals, without adversely affecting coronary blood flow regulation.

Animals↗
PubMed1986

The effects of substance P on the preconstricted pulmonary vasculature of the anesthetized dog.

Substance P is a vasoactive peptide. Nerve fibers containing substance P are present in the media of pulmonary arteries but the physiologic function of substance P in the pulmonary vasculature is unknown. Several doses of substance P were infused intravenously in the anesthetized dog to ascertain its effects on the pulmonary vasculature, both during normoxia and following preconstriction with hypoxia (F1O2 0.1) or prostaglandin F2 alpha (PGF2 alpha 5 mug/kg/min). Substance P resulted in systemic vasodilation during normoxia but had minimal effect on the pulmonary vasculature. During hypoxia and PGF2 alpha-induced pulmonary vasoconstriction, substance P significantly lowered pulmonary artery pressure, pulmonary vascular resistance, mean aortic pressure, and total systemic resistance. It had no effect on cardiac output, wedge pressure, and arterial blood gases. To investigate possible mechanisms for substance P-induced vasodilation, substance P was studied following pretreatment with N-acetylcysteine (a radical scavenging agent), methylene blue (an inhibitor of guanylate cyclase), meclofenamate (a cyclooxygenase inhibitor), and atropine (a muscarinic receptor antagonist). None of these agents impaired substance P-induced vasodilation. Substance P given intravenously is a nonselective vasodilator in the dog but the mechanism of its action remains uncertain.

Acetylcysteine↗
PubMed1988

Potentiated vasoconstrictor response to vasopressin following meclofenamate in conscious rats.

Experiments were performed to test the hypothesis that release of vasodilator cyclooxygenase products may attenuate the systemic and renal vasoconstrictor responses to arginine vasopressin (AVP) in the conscious, chronically instrumented rat. Four groups of animals were studied under the following conditions: (i) AVP infused iv at 2 ng/min for 40 min followed by a 15-min postcontrol; (ii) pretreatment with meclofenamate (3 mg/kg iv) followed by AVP infusion; (iii) meclofenamate pretreatment followed by saline vehicle infusion; and (iv) saline vehicle infusion alone (time control). AVP increased mean arterial blood pressure (MABP) in both meclofenamate-treated (n = 12) and untreated (n = 12) animals; however, the pressor response was significantly greater in animals with cyclooxygenase inhibition. Both heart rate (HR) and cardiac output (CO) (n = 6) fell during AVP infusion, but there were no differences between the meclofenamate-treated and the untreated groups. However, the total peripheral resistance response to AVP was significantly greater in animals treated with meclofenamate than the untreated group. Renal blood flow (RBF) was not affected by AVP infusion alone, but RBF fell significantly in animals given AVP after cyclooxygenase inhibition. The renal vascular resistance response to AVP was also enhanced by cyclooxygenase inhibition. There were no changes in any of the hemodynamic variables in either of the control protocols (i.e., meclofenamate alone or vehicle). These data demonstrate a consistent effect of cyclooxygenase inhibition to augment the systemic and renal vasoconstrictor responses to AVP, and suggest that endogenous vasodilator prostaglandins attenuate the potent vasoconstrictor action of this peptide in vivo.

Animals↗
PubMed1990

Kallidin effect on renal tubular function in meclofenamate- and vehicle-pretreated rats.

The effect of kallidin (lysyl-bradykinin) on the urinary recovery of sodium-22 was examined in anesthetized, volume-expanded rats. Sodium-22 was microinfused into the lumen of late proximal convoluted tubules with and without kallidin (100 pg/ml). Kallidin enhanced mean sodium-22 recovery from a control of 2.24 +/- 0.29% to 6.22 +/- 1.30% (delta = 3.98 +/- 1.31%, P less than 0.005). The urinary recovery of simultaneously microinfused inulin, mean blood pressure, urine flow, and the rate of tubular infusion were similar during control and kallidin microinfusions. Pretreatment of rats with meclofenamate (3.0 mg/kg) to inhibit renal prostaglandin synthesis blunted, but did not abolish, the effect of kallidin to promote sodium-22 recovery. The changes in sodium recovery induced by kallidin represent a 175 +/- 47% and a 58 +/- 11% increase from control values in vehicle- and meclofenamate-pretreated rats, respectively. The results indicate that kallidin, microinfused in high doses into the lumen of late proximal tubules, may lower sodium efflux in that nephron. Inhibition of prostaglandin synthesis reduced the tubular effect of kallidin, suggesting that enhanced prostaglandin synthesis may contribute to the natriuretic effects of kallidin. Alternatively, meclofenamate may directly oppose the tubular effect of kallidin.

Animals↗
PubMed1980

Failure of prostaglandin inhibition to attenuate the tolerance to hemorrhage in domestic chicken.

Domestic fowl have been shown to have the ability to withstand severe hemorrhage. Recent studies in mammals have suggested that prostaglandin hormones may be beneficial during hemorrhagic shock. It has been reported that chickens have high circulating levels of prostaglandins. Anesthetized chickens were stressed by the removal of 45% of the their estimated total blood volume. When compared to controls, neither prostaglandin inhibition with indomethacin or meclofenamate decreased the ability of these animals to tolerate hemorrhage. Changes in mean arterial pressure following hemorrhage were not altered by prostaglandin inhibition. These data demonstrate that prostaglandins are not responsible for the tolerance to hemorrhage observed in domestic fowl.

Animals↗
PubMed1976

Endotoxin and prevention of hypoxic pulmonary vasoconstriction.

Endotoxin is known both to stimulate prostaglandin production and to abolish the pulmonary vascular pressor response to hypoxia. The present study demonstrated that two inhibitors of prostaglandin synthesis, meclofenamate and indomethacin, prevent loss of pulmonary vasoconstriction due to hypoxia when sublethal doses of endotoxin are administered. This suggests that endotoxin may stimulate the production of a dilator prostaglandin which would oppose the hypoxic vasoconstriction, but other ways in which these inhibitor drugs might act are considered. Endotoxin damages platelets and leukocytes, both of which can form prostaglandins and could be the source of a dilator prostaglandin. However, in these experiments endotoxin abolished the hypoxic pressor response in dogs rendered severely thrombocytopenic by platelet antiserum. This suggests that platelets are not involved. In further experiments blood from anesthetized dogs was circulated through glass bead columns. Changes in the leukocyte count following perfusion were correlated with changes in the subsequent pressor response to hypoxia. The possibility that leukocytes may be involved in the effect of endotoxin on the hypoxic pressor response is considered.

Animals↗
PubMed1997

Role of angiotensin II in the renal effects induced by nitric oxide and prostaglandin synthesis inhibition.

The objective of this study was to examine the renal effects of changes in intrarenal angiotensin II levels during the administration of a cyclooxygenase inhibitor, when nitric oxide synthesis is reduced. In the first group of dogs, the administration of meclofenamate and a subpressor dose of L-NAME induced an increase (P < 0.05) in arterial pressure (14 +/- 2 mm Hg), a decrease (P < 0.05) in RBF (180 +/- 13 to 111 +/- 10 mL/min) and GFR (37 +/- 3 to 24 +/- 5 mL/min), and a reduction in the renal excretory response to a sodium load. In the second group, the administration of a converting enzyme inhibitor prevented the increase in arterial pressure, the renal vasoconstriction, and the increase in the proximal but not the distal tubular sodium reabsorption induced by the inhibition of prostaglandins and nitric oxide synthesis. In the third group, it was found that a small increase in the intrarenal angiotensin II levels, which does not produce changes in renal function in control conditions, induced a significant decrease in RBF (183 +/- 14 to 71 +/- 12 mL/min) and GFR (36 +/- 3 to 13 +/- 4 mL/min) when meclofenamate was administered and nitric oxide synthesis was slightly reduced. The results of this study suggest that renal vasoconstriction and increased proximal sodium reabsorption during the reduction of nitric oxide and prostaglandin synthesis are produced by endogenous angiotensin II levels. These results also suggest that endogenous intrarenal nitric oxide and prostaglandins may serve as homeostatic mediators of angiotensin II effects when the intrarenal levels are inappropriately elevated, as occurs in salt-sensitive hypertension.

Analysis of Variance↗
PubMed1999

Role of nitric oxide synthase and cyclooxygenase in pulmonary vascular control in isolated perfused lungs of ferrets, rats and rabbits.

Dilator products of nitric oxide synthase (NOS) and cyclooxygenase (COX) may contribute to the low normal pulmonary artery pressure (Ppa). In isolated perfused lungs of ferrets, rabbits and rats we investigated this hypothesis by blockade of NOS with L-NAME (L-nitro-arginine methyl ester) and COX with meclofenamate. There were species differences. Inhibition of either enzyme caused little rise in Ppa in ferrets and rats but inhibition of both enzymes caused huge increases in Ppa. We suggest this might be due to intracellular connections between the excitatory pathways for NOS and COX dilators, such that inhibition of one enzyme leads to activation of the other. Impairment of these endothelial-based enzymes in pulmonary vascular disease might lead to severe pulmonary hypertension. By contrast, in rabbits, comparable doses of L-NAME lead to large rises in Ppa which were reversed rather than amplified by COX blockade. NO seems to protect against some pressor/oedema forming product of COX in this species.

Animals↗
PubMed1975

Plasma levels following administration of sodium meclofenamate by various routes.

Sodium meclofenamate, an anti-inflammatory and anti-anaphylactic agent, was administered to cattle intravenously, orally and by intraruminal injection. Plasma levels of the free drug were estimated fluorimetrically at intervals after administration by each route. Levels fell rapidly, particularly during the first hour after intravenous injection. Differences between those plasma levels resulting from oral administration and those following intraruminal injection indicated that direct passage into the abomasum was achieved by the former method. Simultaneous intravenous and intrauminal injections achieved immediate high plasma levels and maintained levels adequate for efficacy for 24 h.

Administration, Oral↗