Localization of prostaglandins inhibition of rat renal ammoniagenesis.
Explore the source record for details and available documents.
Ammonia↗
SEARCH · PubMed Health
Results for “Meclofenamic Acid”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Intranephron ammoniagenesis and its regulation by PGE2 in rats and mice.
Explore the source record for details and available documents.
Ammonia↗
Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases.
BACKGROUND: The prevalence of the endothelium-impaired function disorders, such as hypertension and diabetes mellitus, and the severity of their complications are considerably greater in blacks than whites. Evidence has accumulated that superoxide (O2-) production and its interaction with nitric oxide (NO), yielding the strong oxidant peroxynitrite (ONOO-), play central roles in vascular pathophysiology. We hypothesized that the differences in endothelial NO/O2-/ONOO- metabolism may highlight the potential predisposition to endothelial dysfunction and cardiovascular complications prevalent in blacks. METHODS AND RESULTS: Highly sensitive tandem electrochemical NO/O2-/ONOO- nanosensors were positioned in single human umbilical vein endothelial cells (HUVECs) isolated from blacks and whites, and the kinetics of NO/O2-/ONOO- release were recorded in vitro. HUVECs were also analyzed by Western immunoblotting and enzyme activity assays for NAD(P)H-oxidase and endothelial NO synthase (eNOS). Compared with whites, HUVECs from blacks elicited reduced release of bioactive NO with an accompanying increase in the release of both O2- and ONOO-. The greater potency of NO production because of eNOS upregulation in HUVECs from blacks is associated with a decrease in the NO bioavailability. This is due to increased NO degradation by excess O2- produced primarily by 2 enzymatic sources: NAD(P)H-oxidase and uncoupled eNOS. CONCLUSIONS: Compared with whites, the steady-state NO/O2-/ONOO- balance in endothelial cells from blacks is kept closer to the redox states characteristic for the endothelium-impaired function disorders. This may explain the differences in racial predisposition to the endothelium dysfunction during ongoing vascular disturbances with the hallmark of enhanced NO inactivation within the endothelium by oxidative stress.
Acetophenones↗
Reflex responses to myocardial ischemia and reperfusion. Role of prostaglandins.
Powerful vasodepressor and cardioinhibitory reflexes are activated in humans during inferior wall myocardial ischemia or infarction and during restoration of flow to the ischemic region. Experiments in dogs have demonstrated that these responses are due to stimulation of afferent vagal fibers that are located mainly in the inferior wall of the heart. Prostaglandins are released during myocardial ischemia and possibly during reperfusion. Prostaglandins stimulate chemosensitive but not mechanosensitive endings in the ventricles. Our studies determined whether blockade of prostaglandin synthesis with indomethacin or sodium meclofenamate decreased the reflex inhibitory responses to coronary occlusion and reperfusion. Experiments were done in alpha-chloralose-anesthetized dogs after sinoaortic baroreceptor denervation. Occlusion of the circumflex coronary artery for 5 minutes resulted in decreases in arterial pressure and in renal sympathetic nerve activity. During the first 5 minutes after release of the occlusion, renal nerve activity remained inhibited. After treatment with indomethacin (n = 6, 5 mg/kg i.v.) or sodium meclofenamate (n = 3, 4 mg/kg i.v.), coronary occlusion resulted in significantly less inhibition of renal nerve activity. Renal nerve activity returned to control during the first minute of reperfusion. In six additional experiments the responses to coronary occlusion and reperfusion were not altered by treatment with vehicle. Our data suggest that prostaglandins serve as the major stimulus to ventricular sensory endings during myocardial ischemia and reperfusion. Our data further suggest that reflex inhibitory responses during ischemia and reperfusion are due mainly to stimulation of chemosensitive endings.
Afferent Pathways↗
Effects of exogenous heme on renal function: role of heme oxygenase and cyclooxygenase.
We examined the effects of heme administration (15 mg/kg IV) on indexes of renal carbon monoxide production and contrasted the renal functional response to heme in anesthetized rats pretreated and not pretreated with stannous mesoporphyrin (40 micromol/kg IV) to inhibit heme oxygenase or sodium meclofenamate (5 mg/kg IV plus infusion at 10 microg/kg per minute) to inhibit cyclooxygenase. In rats without drug pretreatment, heme administration decreased renal vascular resistance and increased renal blood flow, urine volume, and sodium excretion associated with augmented urinary excretion of 6-keto-PGF1alpha and enhanced concentration of carbon monoxide in the renal cortical microdialysate. Pretreatment with stannous mesoporphyrin did not prevent heme from producing renal vasodilation and increasing renal blood flow but abolished the diuretic and natriuretic responses. Conversely, pretreatment with sodium meclofenamate blunted the renal vasodilatory effect of heme but affected neither the diuretic nor the natriuretic effect. We conclude that heme-induced renal vasodilation is a cyclooxygenase-dependent response involving increased synthesis of PGI2, whereas heme-induced diuresis and natriuresis are heme oxygenase-dependent responses involving inhibition of tubular reabsorption of sodium and water through undefined mechanisms.
Animals↗
Interactions between vasoconstrictors and vasodilators in regulating hemodynamics of distinct vascular beds.
We examined whether interactions between angiotensin II (Ang II), endothelin (ET), nitric oxide (NO), and prostaglandins (PGs) differentially regulate perfusion to distinct vascular beds. For this, we blocked either angiotensin AT1 or ET receptors or both and then sequentially inhibited NO and PG synthesis in anesthetized dogs. Blocking Ang II or ET had similar effects on systemic hemodynamics: Mean arterial pressure fell slightly without altering cardiac output. Blocking both caused a synergistic fall in mean arterial pressure and increased cardiac output. Pulmonary vascular resistance was not altered by blocking Ang II, ET, or both but progressively increased during NO and PG blockade in group 2 (which had unblocked ET receptors), suggesting that endogenous ET exerts pulmonary vasoconstriction that is tempered by NO and PGs. In the kidney, blocking Ang II increased regional blood flow (RBF), glomerular filtration rate (GFR), and fractional excretion of sodium (FENa). In contrast, blocking ET did not alter RBF, and it decreased GFR and FENa. Combined Ang II and ET blockade markedly increased RBF without altering GFR, and FENa was maintained at the levels as when only ET was blocked. Sequentially inhibiting NO and PGs decreased RBF when Ang II or ET were blocked but had little effect when both were blocked. Finally, Ang II or ET blockade did not alter iliac blood flow. Inhibiting NO and PGs decreased iliac blood flow when Ang II or ET but not both were blocked. These results suggest that regional differences in the interactions between endogenous Ang II, ET, NO, and PGs are important determinants in systemic, pulmonary, and regional hemodynamics.
Angiotensin II↗
Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat.
The angiotensin antagonist, saralasin, (10 and 30 mg/kg), increased serum renin activity (SRA) in normal, conscious rats from 2.7 +/- 0.4 to 16.2 +/- 3.7 and 22.5 +/- 2.4 ng/ml/hr (p less than 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E2 (PGE2) by 75%, and arachidonate-induced hypotension by 83%, failed to alter basal SRA but inhibited saralasin-induced renin release by 99% and 87% at the 10 and 30 mg/kg doses, respectively. Indomethacin failed to alter basal hemodynamics or the hemodynamic response to saralasin. Propranolol (1.5 mg/kg) inhibited saralasin-induced renin release by 93% and enhanced the suppressant effect of indomethacin from 79% to 100%. Meclofenamate, another prostaglandin synthesis inhibitor, also blocked saralasin-induced renin release by 99% and 72% at the 10 and 30 mg/kg doses, respectively (p less than 0.001). In sodium-depleted rats, saralasin (0.3 mg/kg) increased SRA from 12 +/- 2 to 119 +/- 6 ng/ml/hr (p less than 0.001) and decreased blood pressure by 6% (p less than 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE2 by 79%, and arachidonate-induced hypotension by 81%. These findings suggest 1) that saralasin-induced renin release is mediated by renal prostaglandins, and 2) an interrelationship exists between the receptor controlling AII-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor.
Animals↗
Suppression of angiotensin II release by prostaglandin synthesis inhibitors in hind legs.
Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused rat mesenteric arteries was mediated by beta-adrenergic receptor activation. However, the precise mechanism of regulation of vascular renin-angiotensin is not completely understood. In this study, we examined the effect of indomethacin and meclofenamate on immunoreactive angiotensin I (Ang I) and immunoreactive Ang II release from perfused rat hind leg vasculature to delineate the possible relevance of prostaglandins to the vascular renin-angiotensin system in vitro. We also examined the effects of isoproterenol and propranolol on the immunoreactive Ang I and II release. Isolated rat hind legs were perfused with Krebs-Ringer solution, and immunoreactive Ang I and II released into the perfusate were measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Indomethacin and meclofenamate (10(-8) to 2 X 10(-6) M) added to the perfusion medium suppressed immunoreactive Ang I and II release to similar extents in a dose-dependent manner (p less than 0.001); the maximal percent inhibition of immunoreactive Ang II release evoked by these inhibitors (2 X 10(-6) M) was 60 +/- 6% (p less than 0.001) for indomethacin and 50 +/- 4% (p less than 0.001) for meclofenamate. Isoproterenol (10(-6) M) failed to cause a change in the release of both peptides, but propranolol (10(-6) M) slightly decreased the release of immunoreactive Ang I and II by 28 +/- 4% (p less than 0.001) and 32 +/- 4% (p less than 0.001), respectively. There was a highly significant positive correlation between the released amount of immunoreactive Ang I and that of immunoreactive Ang II altered by indomethacin (r = 0.91), meclofenamate (r = 0.94), or propranolol administration (r = 0.90). These results suggest that the renin-angiotensin in the hind legs is modulated by prostaglandins and that a difference exists in the beta-adrenergic receptor-mediated release of Ang II among diverse vascular beds.
Angiotensin I↗
Role of prostaglandins in mediating the renal effects of atrial natriuretic factor.
The natriuretic response to the intrarenal administration of atrial natriuretic factor (ANF) is accompanied by an increase in the synthesis of prostaglandins and by a redistribution of renal blood flow from the superficial to the deep cortex. This study was undertaken to define whether prostaglandins mediate the ANF-induced redistribution of renal blood flow and if prostaglandins and renal blood flow redistribution contribute to the natriuretic actions of ANF. In anesthetized dogs, the intrarenal administration of indomethacin (10 micrograms/kg/min) or the intravenous administration of meclofenamate (5 mg/kg) completely prevented the sixfold and twofold increments in urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, respectively; it also abolished the redistribution of renal blood flow to the deep cortex. However, ANF induced a similar natriuresis before (from 53 +/- 17 to 281 +/- 48 microEq/min) and after (from 45 +/- 13 to 273 +/- 60 microEq/min) the administration of prostaglandin synthesis inhibitors. It is concluded that the ANF-induced redistribution of renal blood flow to the deep cortex is prostaglandin-mediated but that neither redistribution nor increased prostaglandin synthesis is an important mediator of ANF's natriuretic action.
6-Ketoprostaglandin F1 alpha↗
Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin.
Intracerebroventricular infusion of the peptide melittin increases immunoreactive kinins in the cerebrospinal fluid of anesthetized dogs, probably secondary to activation of brain or cerebrospinal fluid kininogenases. Intracerebroventricular melittin also increases blood pressure and heart rate, possibly mediated by brain kinins, since intracerebroventricular bradykinin also increases blood pressure and heart rate. We tested whether the effects of centrally administered melittin on blood pressure and heart rate could be blocked by simultaneous infusion of a kinin receptor antagonist, [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin, in normotensive awake rats. In the controls, intracerebroventricular infusion of kinin receptor antagonist given for 1 hour at a rate of 10 micrograms/hr blocked bradykinin-induced increases in blood pressure and heart rate by 80%. Basal blood pressure and heart rate were not affected by the kinin receptor antagonist alone. After a 30-minute infusion of melittin (8 micrograms/30 min), cerebrospinal fluid kininogenase activity (n = 17) rose from 0.13 +/- 0.05 to 0.43 +/- 0.1 ng/ml/min (p less than 0.02). Although cerebrospinal fluid kinins increased from below sensitivity (0.02 ng/ml, n = 12) to 0.19 +/- 0.1 ng/ml (n = 17), this change was due to drastic increases in three rats, whereas in 12 of them kinins were below sensitivity. Incubation of bradykinin (10 ng) with 0.1 ml rat cerebrospinal fluid for 5 minutes destroyed 70% of kinins, suggesting that rapid destruction may have made detection of increased CSF kinins difficult.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Influence of prostaglandins on papillary blood flow and pressure-natriuretic response.
The present study examined whether renal prostaglandins influence the pressure-natriuretic response by altering medullary hemodynamics or renal interstitial pressure. The diuretic and natriuretic responses to changes in renal perfusion pressure were compared in control rats (n = 15) and in rats receiving either meclofenamate (2 mg/kg, n = 9) or indomethacin (2 mg/kg, n = 4). In control rats, urine flow and sodium excretion increased from 10 +/- 2 to 118 +/- 10 microliters/min/g kidney wt and from 1.8 +/- 0.3 to 21.0 +/- 1.5 mueq/min/g kidney wt, respectively, when renal perfusion pressure was increased from 109 to 167 mm Hg. Urinary excretion of prostaglandin E2 and thromboxane B2 increased significantly by 152% and 190%, respectively. Meclofenamate lowered thromboxane B2 and prostaglandin E2 excretion and prevented the increase in eicosanoid excretion produced by elevations in perfusion pressure. The pressure-diuretic and pressure-natriuretic responses of rats given meclofenamate or indomethacin were approximately half of those observed in the control rats. Papillary blood flow increased 21% and renal interstitial pressure rose from 5.0 +/- 0.7 to 8.2 +/- 0.7 mm Hg in control rats when pressure was elevated from 100 to 150 mm Hg. Meclofenamate and indomethacin lowered papillary blood flow and renal interstitial pressure and blunted the increases in these values produced by elevations in perfusion pressure. These results support the view that renal prostaglandins modulate the pressure-natriuresis relation by altering renal medullary hemodynamics and suggest that an intact renal prostaglandin system is necessary for the full expression of the medullary hemodynamic and natriuretic responses to increases in renal perfusion pressure.
Animals↗
Effects of NG-monomethyl-L-arginine and L-arginine on acetylcholine renal response.
Intrarenal infusion of acetylcholine in meclofenamate-treated dogs significantly increased renal blood flow, diuresis, and natriuresis. Intrarenal infusions of either NG-monomethyl-L-arginine (inhibitor of endothelium-derived relaxing factor formation), or L-arginine (precursor of endothelium-derived relaxing factor formation) did not modify basal levels of those parameters. However, the infusion of NG-monomethyl-L-arginine inhibited the acetylcholine-induced increases in renal blood flow and diuresis without affecting natriuresis, which increased significantly. The infusion of L-arginine failed to further enhance hemodynamic and excretory effects elicited by acetylcholine. The concomitant infusion of L-arginine and NG-monomethyl-L-arginine did not change renal blood flow, urine flow, or sodium excretion rate. L-Arginine administration prevented the inhibitory effect of NG-monomethyl-L-arginine on acetylcholine-induced renal vasodilatation and diuresis. Glomerular filtration rate and mean arterial pressure did not change throughout the experiment. The results indicate that the vasodilatory and diuretic responses to intrarenal acetylcholine in meclofenamate-treated dogs are largely dependent on endothelium-derived relaxing factor.
Acetylcholine↗
Long-term cardiovascular role of nitric oxide in conscious rats.
The goal of this study was to determine the arterial pressure and renal excretory responses to a continuous intravenous infusion of 7.4 nmol/kg per minute of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in conscious rats. Studies were conducted in six groups of Sprague-Dawley rats with indwelling arterial and venous catheters over periods lasting 12 to 26 days. In the first group of rats, L-NAME infusion for 9 days caused a sustained increase in arterial pressure, and on the ninth day arterial pressure was increased 29 mm Hg. Infusion of L-NAME at the higher dose of 37 nmol/kg per minute for 9 days caused no greater increase in arterial pressure than the lower dose. Sodium and volume balances and phenylephrine pressor sensitivity were unchanged during L-NAME administration at 7.4 nmol/kg per minute; plasma renin activity increased 2.5-fold, but the vasodepressor and vasodilator responses to acetylcholine and bradykinin were unchanged. Arterial pressure remained significantly increased 7 days after L-NAME was stopped, but in another group of rats, intravenous L-arginine infusion caused arterial pressure to return to control within 1 day. This same dose of L-arginine was administered for 7 days intravenously, and neither arterial pressure nor sodium balance changed. In other groups of rats, L-arginine was administered in conjunction with L-NAME; this prevented any change in arterial pressure, whereas D-arginine did not. In conclusion, the data suggest that continuous intravenous infusion of L-NAME causes sustained increases in arterial pressure in conscious rats without any sodium or water retention. The hypertension is accompanied by increases in plasma renin activity and can be prevented with intravenous L-arginine administration.
Animals↗
Role of endogenous prostaglandins in volume expansion and during furosemide infusion in conscious dogs.
The renal effects of two structurally dissimilar inhibitors of prostaglandin synthesis (Meclofenamate and RO-20-5720) were studied in conscious, chronically instrumented dogs during mild volume expansion and during a constant infusion of furosemide. When either inhibitor was administered following volume expansion, urinary excretion of PGE2 and urine flow rate were reduced by more than 50%. In contrast, renal plasma flow fell by less than 10% while glomerular filtration rate, sodium excretion, and plasma renin activity (PRA) were unchanged. In separate studies, infusion of furosemide increased renal plasma flow, urine flow rate, sodium excretion, PRA, and urinary excretion of PGE2, while glomerular filtration rate decreased. Administration of inhibitors of prostaglandin synthesis during constant infusion of furosemide reduced the urinary excretion of PGE2 to control levels, as renal plasma flow and glomerular filtration rate fell below control level. Despite these hemodynamic alterations, the furosemide-induced diuresis and increase in PRA were only partly attenuated by prostaglandin inhibition. It is concluded that in conscious dogs, intrarenal prostaglandins modulate urine flow rate during mild volume expansion and play a major role in mediating the renal hemodynamic effects of furosemide.
Animals↗
Renal changes induced by nitric oxide and prostaglandin synthesis reduction: effects of trandolapril and verapamil.
The benefits of the simultaneous administration of low doses of a calcium antagonist and a converting enzyme inhibitor in the treatment of hypertension and renal vasoconstriction are well established. The objective of this study was to evaluate whether the administration of low doses of a calcium antagonist and a converting-enzyme inhibitor have beneficial effects in treating the renal alterations induced by the acute administration of a cyclooxygenase inhibitor when nitric oxide synthesis is reduced. These effects were examined in anesthetized dogs before and during an acute sodium load. It was found that the intrarenal infusion of meclofenamate (5 microg x kg[-1] x min[-1]), simultaneously with a low dose of NG-nitro-L-arginine methyl ester (1 microg x kg[-1] x min[-1]), produced a 40% decrease of renal blood flow and glomerular filtration rate and a reduction in the renal excretory response to the sodium load. In a second group of dogs, intrarenal verapamil (0.5 microg x kg[-1] x min[-1]) was effective in blocking the effects of nitric oxide and prostaglandin synthesis inhibition on sodium excretion and glomerular filtration rate but did not modify the effects on renal blood flow. An intrarenal infusion of trandolapril (0.3 microg x kg[-1] x min[-1]) was effective in a third group of dogs in reducing the renal hemodynamic effects but not in preventing the antinatriuretic effect observed in the first group. Finally, in a fourth group, the simultaneous administration of verapamil and trandolapril was effective in treating all the renal changes induced by the cyclooxygenase inhibitor when nitric oxide synthesis was reduced. These results suggest that the combination of low doses of trandolapril and verapamil has additive effects in treating the renal vasoconstriction and antinatriuresis induced by the acute administration of a cyclooxygenase inhibitor, when nitric oxide synthesis is reduced.
Angiotensin-Converting Enzyme Inhibitors↗
Role of nitric oxide and prostaglandins in the long-term control of renal function.
Previous studies have reported evidence of an important interaction between nitric oxide (NO) and prostaglandins in the acute regulation of renal function. The objective of this study was to determine in conscious dogs whether the renal effects of the prolonged administration of a cyclooxygenase inhibitor are enhanced when NO synthesis is reduced. Meclofenamate infusion (5 microg x kg(-1) x min(-1)) during 4 consecutive days (n=8) elicited a continuous decrease (P<0.05) in renal blood flow and plasma renin activity and a transitory decrease in sodium excretion. NG-Nitro-L-arginine methyl ester (L-NAME) infusion (5 microg x kg(-1) x min(-1)) during 6 days (n=8) produced a significant increase in arterial pressure and a transitory decrease (P<0.05) in both renal blood flow and plasma renin activity. The simultaneous inhibition of NO and prostaglandin synthesis (n=7) led to an increase in arterial pressure and a decrease in renal blood flow similar to those observed during the administration of either L-NAME or meclofenamate. In contrast, this simultaneous inhibition produced a decrease in glomerular filtration rate, which was not observed in the previous groups, and also induced an increase in renal vascular resistance and a decrease in sodium excretion greater (P<0.05) than those found during the inhibition of either NO or prostaglandins. Only a transitory decrease in plasma renin activity was found during meclofenamate infusion in this group. The results of this study present new evidence that the renal vasoconstrictor and antinatriuretic effects induced by the prolonged infusion of a cyclooxygenase inhibitor are significantly enhanced when NO synthesis is reduced. These results suggest that renal function may be more sensitive to the prolonged administration of a cyclooxygenase inhibitor in situations where NO production is reduced.
Animals↗
The conscious instrumented rabbit: a model for the study of mechanisms of blood pressure regulation during pregnancy.
Conscious pregnant and nonpregnant rabbits were used to further evaluate the role of prostaglandin (PG) and plasma renin activity (PRA) in the systemic hemodynamics of pregnancy. Pregnant rabbits had high peripheral blood levels of both PGE2 and PRA. Systemic blood pressure was not affected in either pregnant or nonpregnant by the administration of an inhibitor of prostaglandin synthesis. Pregnant rabbits, however, had a much larger decrease in blood pressure than nonpregnant animals when given the angiotensin I (AI)-converting-enzyme inhibitor, captopril. Pregnant rabbits were more resistant to the pressor effect of exogenous AII than nonpregnant animals. The pressor effect of AII increased in pregnant rabbits after the administration of meclofenamate and parturition but was not changed by volume expansion. In contrast, the sensitivity of nonpregnant rabbits to AII increased after volume expansion, but not after treatment with inhibitors of prostaglandin synthesis. These studies demonstrate that a remarkable similarity exists between pregnant rabbits and pregnant women in the pressor response to AII. This study is the first to correlate the vasopressor response to AII with PRA and the level of a circulating vasopressor prostaglandin in pregnant animals. The results strongly suggest that this model will be fruitful in further attempts to define the factors controlling systemic hemodynamics during pregnancy.
Angiotensin II↗
Platelet activating factor vasoconstriction of dog kidney. Inhibition by alprazolam.
Systemic administration of platelet activating factor (PAF; acetyl glyceryl ether phosphorylcholine) reduces renal blood flow, but the mechanism responsible for that effect has not been defined. To address that problem, we determined the effects on renal blood flow of PAF administered directly into the renal artery in pentobarbital (30 mg/kg)-anesthetized dogs. Bolus injections of PAF (0.2-0.8 microgram) caused transient renal vasoconstriction, reducing renal blood flow by 20 to 60% without altering systemic blood pressure; lyso-PAF (1 microgram) had no effect. The effects of PAF on renal blood flow were not altered by alpha-adrenergic blockade (phentolamine, 3 mg/kg) or by angiotensin II receptor blockade ([Sar1,Ala8]angiotensin II, 6 micrograms/kg/min), but they were increased in magnitude and duration by meclofenamate (5 mg/kg), a cyclooxygenase inhibitor. Methysergide (3 mg/kg), a serotonin antagonist, slightly reduced PAF effects, but a specific blocker of vascular serotonin receptors did not. Renal venous plasma platelet density was not altered by infusion of PAF into the renal artery at a dose (1-2 micrograms/min) that caused a sustained 20% renal blood flow decrease. Alprazolam, a benzodiazepine that competitively inhibited PAF-induced aggregation in canine platelet-rich plasma, also inhibited the renal vasoconstrictor action of PAF (0.8 mg/min, into the renal artery) but did not alter renal vasoconstrictor effects of norepinephrine or angiotensin II.
Alprazolam↗