Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Methoxamine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effects of methoxamine and phenylephrine on left ventricular contractility in rabbits.

The end-systolic pressure-volume relation is employed to evaluate left ventricular contractility. In clinical studies, pharmacologic vasoconstriction is used to increase left ventricular systolic pressure to assess pressure-volume relations. However, the effect of vasoconstrictors on the ventricular contractile state is not well characterized. The effects of methoxamine and phenylephrine on systemic arterial pressure and left ventricular contractility in rabbits were studied with three protocols. In protocol 1, anesthetized rabbits (n = 10) were injected with incremental doses of methoxamine and phenylephrine intravenously. Methoxamine (4 mg) increased the mean arterial pressure by 50 +/- 12% (mean +/- SE) (n = 5, p = 0.001). Phenylephrine (0.2 mg) increased mean arterial pressure by 82 +/- 14% (n = 5, p = 0.004). In protocol 2, isolated blood-perfused hearts were injected with incremental doses of these drugs in the ascending aorta in amounts approximately equal to the concentrations injected in the intact rabbits. Methoxamine (2 mg) reduced isovolumic peak systolic left ventricular pressure by 43 +/- 9% (n = 7, p = 0.003), whereas phenylephrine (0.1 mg) increased the isovolumic pressure by 24 +/- 9% (n = 7, p less than 0.05). These responses indicated an enhanced contractile state with phenylephrine and a reduced contractile state with methoxamine. Pretreatment with propranolol blunted the effect of phenylephrine on isovolumic pressure (n = 6, p less than 0.02). In protocol 3, cross-circulation experiments allowed study of the effect of these drugs on isovolumic left ventricular pressure in the isolated heart and simultaneously on the systemic arterial pressure in the intact anesthetized rabbit (support rabbit).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The roles of methoxamine and norepinephrine in electromechanical dissociation.

Electromechanical dissociation (EMD) in patients in cardiac arrest is associated with a poor prognosis. Pressor agents, particularly alpha-agonists, have proven to be useful in resuscitation from asphyxial and fibrillatory arrest in the animal model. Beta-agonists, such as isoproterenol, have not been shown to improve the resuscitation rate. The standard pressor used in all forms of cardiac arrest is epinephrine. The key question that must be considered is whether methoxamine or norepinephrine is superior to epinephrine in resuscitating patients in cardiac arrest. Methoxamine is a pure alpha 1 agonist causing vasoconstriction and increased peripheral vascular resistance. Norepinephrine and epinephrine demonstrate activity at alpha 1, alpha 2, beta 1, and beta 2 receptor sites. Does alpha 2 and beta activity help or hinder resuscitation? Beta activity on the myocardium will increase oxygen consumption (inotropic and chronotropic effects), may predispose to arrhythmias, and will shunt blood from the endocardium to the epicardium. On the other hand, there is evidence that beta agonists increase coronary and cerebral blood flow. Outcome studies have shown methoxamine to be comparable to epinephrine in resuscitation from asphyxial arrest. One study demonstrated methoxamine's superiority in raising the aortic diastolic pressure and resuscitating animals from ventricular fibrillation. No significant advantage of norepinephrine use is evident in the literature. Controlled experiments in the animal model and in human patients must be done to determine whether methoxamine or epinephrine is superior in resuscitation from EMD and other forms of cardiac arrest.

Animals↗
PubMed1987

Methoxamine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

The improvement in cerebral blood flow (CBF) during CPR after epinephrine administration has been attributed to epinephrine's alpha-adrenergic properties. Methoxamine, a pure alpha-1 agonist, has only been shown to be comparable to epinephrine in restoring circulation after cardiac arrest in a canine model. This study compares the effectiveness of equipotent doses of epinephrine and methoxamine in improving CBF during CPR after a prolonged cardiac arrest in a swine model. Twenty-five swine, weighing 15.9 to 28.2 kg, underwent instrumentation for regional CBF using tracer microspheres. CBF was determined during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun with a pneumatic compressor. CBF measurements were again made during CPR. After 3 min of CPR, the swine were randomized to receive 0.02 or 0.2 mg/kg epinephrine, 0.1, 1.0, or 10.0 mg/kg methoxamine. Five swine were allocated to each group. CBF measurements were determined after drug administration and compared using a Bonferroni multiple comparison procedure. A p-value less than .05 was considered statistically significant. This study demonstrated that, after a 10-min cardiac arrest, CBF was extremely low, averaging less than 7 ml/min X 100 g during external CPR. There were no clinically significant improvements in regional CBF after 0.02 mg/kg of epinephrine, or the two lowest doses of methoxamine. The addition of 10 mg/kg of methoxamine clinically improved blood flow only to the most caudal CNS structures, including the pons, medulla, and cervical spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Epinephrine versus methoxamine in survival postventricular fibrillation and cardiopulmonary resuscitation in dogs.

Previous studies have indicated that methoxamine (an alpha adrenergic receptor agonist) may provide an advantage compared to epinephrine (a mixed alpha and beta adrenergic agonist) during cardiac arrest and CPR. To test this theory, we compared the effects of bolus injections of epinephrine vs. methoxamine on survival, hemodynamic variables, blood gases, and blood lactate concentrations during ventricular fibrillation and CPR in 12 dogs. Each dog underwent a 3-min fibrillatory arrest followed by 10 min of fibrillation and CPR, at which time the animals were defibrillated. Epinephrine (0.05 mg/kg, n = 6) or methoxamine (2 mg/kg, n = 6) was administered at the start of CPR. Both epinephrine and methoxamine produced identical survival rates (5/6) with no differences in coronary perfusion pressure gradients or blood gases (aortic, venous, or great cardiac venous pH, PaO2, or PaCO2) during CPR. Also, there were no differences between the two study groups in myocardial lactate or oxygen extraction ratios during CPR. We conclude that in the dosages tested in our experimental model, epinephrine and methoxamine produce similar results in the variables which we measured.

Animals↗
PubMed1981

Regional oxygen consumption and supply in heart: effect of methoxamine-induced pressure rise.

The effect of raising arterial blood pressure 50 mmHg with methoxamine on regional left ventricular O2 supply and consumption was studied in 27 pentobarbital-anesthetized open-chest rabbits. Three groups of animals were studied: 1) control, 2) methoxamine infusion sufficient to raise pressure 50 mmHg, and 3) methoxamine infusion sufficient to raise pressure 50 mmHg with atrial pacing to maintain heart rate. Subepicardial (epi) and subendocardial (endo) O2 saturations were determined with a microspectrophotometric technique. Regional flow was determined with radioactive microspheres and regional O2 consumption by the Fick principle. In the control group, endo venous O2 saturation [31 +/- 3% (SE)] was lower than epi (42 +/- 2%). There were no significant regional differences in blood flow (avg 128 +/- 2 ml . min-1 . 100 g-1). With methoxamine when heart rate fell, there were no differences in regional flow or consumption when compared to control. During methoxamine infusion, when heart rate was maintained, there was higher coronary blood flow (361 +/- 52 ml . min-1 . 100 g-1) and O2 consumption (27 +/- 4 ml O2 . min-1 . 100 g-1). No regional differences, epi vs. endo, were found in this group. After a 50-mmHg pressure rise, the endo region of the left ventricle had an increased O2 consumption mediated by an increased coronary blood flow without a significant rise in O2 extraction, similarly to epi.

Animals↗
PubMed1975

Positive inotropic effects of methoxamine: evidence for alpha-adrenergic receptors in ventricular myocardium.

The present study was undertaken to evaluate the effects of methoxamine on force development and adenyl cyclase activity in cat ventricular myocardium. Methoxamine produced a dose-related increase in force development of isometrically contracting cat papillary muscles. The positive inotropic effects of methoxamine were not altered by beta-adrenergic blockade (propranolol), or catecholamine depletion by prior reserpinization, but were completely prevented by alpha-adrenergic blockade (phentolamine or ergotamine). Neither ergotamine, phentolamine, nor methoxamine had any direct effects on adenyl cyclase activity. Phentolamine did not attenuate the increase in force development produced by paired electrical stimulation, suggesting that it does not block the entry of calcium into the muscle. In summary, methoxamine produced a dose-related increase in force development of the cat papillary muscle that was selectively blocked by alpha-adrenergic receptors in ventricular myocardium.

Adenylyl Cyclases↗
PubMed1979

Cyclic adenosine 3',5'-monophosphate in rat cerebral cortical slices: effects of methoxamine and clonidine.

In incubated slices of cerebral cortex from Sprague-Dawley rats, methoxamine and clonidine have no effect on basal levels of cyclic AMP. Methoxamine effectively inhibits the noradrenaline-stimulated formation of cyclic AMP. The inhibitory constant for methoxamine was 12.6 mumol/l. In the presence of 100 mumol/l adenosine, methoxamine does not inhibit the activity of noradrenaline, but is capable to activate alpha-adrenergic receptors leading to enhanced formation of cyclic AMP. The mechanism by which adenosine alters adrenergic receptors to become methoxamine-sensitive is not known. Clonidine inhibits the effect of noradrenaline alone or in combination with adenosine on the cyclic-AMP-generating system. It does not, as reported earlier, enhance the activity of submaximal concentrations of the beta-adrenergic agonist isoproterenol. These data do not support the concept of adrenergic receptors which require both, alpha- and beta-stimulation for maximal activation of adenylate cyclase.

Adenosine↗
PubMed1985

Effect of methoxamine on spontaneous motility of the isolated rat uterus.

In the present study the effect of methoxamine and its modification by several adrenergic antagonists is described in the isolated oestrogenized rat uterus. Methoxamine produced a dose-related increase in uterine activity, prazosin produced a rightward displacement of the dose-response curve of methoxamine reaching the same maximal effect. Yohimbine abolished the contractile response to methoxamine. propranolol or reserpine failed to modify the effect of methoxamine. Pretreatment with reserpine abolished the inhibitory effect of yohimbine. These results suggest the presence of excitatory alpha-adrenoceptors in the rat uterus.

Adrenergic alpha-Agonists↗
PubMed1995

Effects of pretreatment with inhaled methoxamine on bronchial responses to histamine in asthmatic subjects.

The underlying mechanisms of bronchial obstruction in asthma are complex. Both bronchospasm and bronchial oedema are thought to play pivotal roles in asthma, but their respective importance in a given asthmatic individual is unknown. To address this question, we assessed the effects of pretreatment with inhaled methoxamine, a potent alpha 1-adrenoceptor agonist, on bronchial response to inhaled histamine in 10 asthmatic subjects. The study was conducted according to a double-blind, cross-over, randomized and placebo-controlled design. In each subject, dose-response curves for the effects on forced expiratory volume in one second (FEV1) of serially doubling doses of inhaled histamine were obtained on three different days, 15 min after pretreatment with either methoxamine (10 mg) or duplicated placebo. Histamine, first dose 100 micrograms (543 nmol), was delivered by a breath-activated dosimeter every 5 min. FEV1 was measured in triplicate after each dose and the largest value was retained. There was no difference in baseline and prechallenge FEV1 after placebo and methoxamine. Mean coefficient of variation of decrease in FEV1 induced by histamine on the two placebo days was 6.7 +/- 2%. On average, the bronchial responses to histamine were not modified by pretreatment with methoxamine as compared to placebo (delta FEV1 = 0.83 +/- 0.14 l on methoxamine versus 0.85 +/- 0.11 l and 0.86 +/- 0.13 l on the two placebo days).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1989

Glycogen phosphorylase activation by two different alpha 1-adrenergic receptor subtypes: methoxamine selectively stimulates a putative alpha 1-adrenergic receptor subtype (alpha 1a) that couples with Ca2+ influx.

We compared the effects of methoxamine on alpha 1-adrenergic receptor-mediated phosphorylase activation in rat hepatocytes and rabbit aorta. Although methoxamine is a potent agonist in activating phosphorylase of rabbit aorta, it had little effect in rat hepatocytes. Using the phenoxybenzamine inactivation method, we found that the quantitative relationship between 125I-BE2254 (125I-BE) binding capacity and maximal norepinephrine-stimulated phosphorylase activation was nonlinear in rabbit aorta, whereas it was linear in rat hepatocytes. The potency of methoxamine in inhibiting specific 125I-BE binding is significantly (p less than 0.05) higher in rabbit aorta (Kd, 96.4 +/- 7.7 microM), compared with rat hepatocytes (Kd, 283 +/- 16 microM). However, these quantitative differences could not fully explain the blunted [Ca2+]c and phosphorylase responses to methoxamine in rat hepatocytes. Treatment with chlorethylclonidine dose dependently suppressed 125I-BE binding sites and norepinephrine-induced phosphorylase activation in rat hepatocytes, whereas in rabbit aorta it resulted in only a 31% decrease in 125I-BE binding sites, with little effect on phosphorylase activation. Furthermore, alpha 1-adrenergic receptor-mediated cellular events of phosphatidylinositol (PI) hydrolysis and phosphorylase activation were unaffected by the removal of extracellular Ca2+ in rat hepatocytes, whereas both responses were markedly attenuated in rabbit aorta. The results indicate that two different alpha 1-adrenergic receptor subtypes activate glycogen phosphorylase, through different mechanisms for increasing [Ca2+]c in the two systems. In rat hepatocytes, alpha 1 receptors are closely linked to PI hydrolysis and Ca2+ release from intracellular stores and cause phosphorylase activation. In rabbit aorta, on the other hand, activation of alpha 1 receptors increases [Ca2+]c by Ca2+ influx from the extracellular fluid as well as by Ca2+ release, and both PI hydrolysis and phosphorylase activation are caused mainly by the Ca2+ entry. Methoxamine interacts with both chlorethylclonidine-sensitive and -insensitive alpha 1 receptor subtypes but selectively stimulates the alpha 1 receptor subtype that closely couples with the Ca2+ influx.

Animals↗
PubMed1980

Comparison of the alpha-adrenergic agonists, phenylephrine and methoxamine in rabbit papillary muscles.

The positive inotropic effects of the alpha-adrenergic agonists, phenylephrine and methoxamine were compared in isolated rabbit papillary muscles. Phenylephrine in the presence of 10(-7)M propranolol produced a greater response than methoxamine. Antagonism by phentolamine was competitive for phenylephrine and apparently, noncompetitive for methoxamine. Based upon observed maximum following frequencies, 10(-4)M methoxamine had a greater cardiac depressant effect than 10(-4) phenylephrine. It was suggested that phenylephrine with a beta-adrenergic antagonist possessed advantages over methoxamine as an agonist for studying cardiac alpha-adrenergic receptors in rabbit papillary muscles.

Animals↗
PubMed1996

Intracoronary administration of the alpha 1-receptor agonist, methoxamine, does not reproduce the infarct-limiting effect of ischemic preconditioning in dogs.

BACKGROUND: The cardioprotective effect of ischemic preconditioning has been hypothesized to occur through one or more signalling mechanisms which activate protein kinase C. Stimulation of alpha 1-adrenergic receptors by catecholamines released during the preconditioning episodes of ischemia is one of these putative signalling mechanisms. METHODS: To determine whether stimulation of alpha 1-adrenergic receptors before an ischemic challenge can mimic preconditioning, anesthetized dogs were treated with 4 intracoronary infusions of methoxamine HCl (10 micrograms/kg/min; n = 8), each 5 min in duration and followed by 5 min of washout. Control dogs (n = 10) were given similar infusions of 0.9% NaCl. A third group of dogs was preconditioned with 4 cycles of 5 min ischemia, each followed by 5 min of reperfusion (n = 8). All dogs then underwent 60 min of ischemia (circumflex coronary occlusion) followed by 3 h of reperfusion. Infarct size (expressed as % of area-at-risk) was measured with TTC macrochemistery and analyzed (using analysis of covariance [ANCOVA]) with respect to coronary collateral blood flow (measured using radioactive microspheres). RESULTS: Methoxamine markedly increased systemic arterial and left atrial pressures prior to but not during the ischemic challenge. Baseline predictors of infarct size were not different among the groups. Mean infarct size (adjusted from ANCOVA) did not differ between control and methoxamine-treated groups, 28.3 +/- 2.8% vs. 29.7 +/- 3.2%, respectively (P = NS), but was only 12.7 +/- 3.2% in the preconditioned group (P < 0.01 vs. control and methoxamine). CONCLUSIONS: A series of methoxamine infusions before an ischemic challenge did not affect infarct size. Thus, stimulation of alpha 1-adrenergic receptors alone is insufficient to mimic the cardioprotective effect of ischemic preconditioning in this canine model.

Adrenergic alpha-Agonists↗
PubMed1996

The opposite effects of amitriptyline on noradrenaline- and methoxamine-evoked venoconstriction in man.

The effects of a single oral dose (100 mg) of amitriptyline on noradrenaline- and methoxamine-evoked venoconstriction were compared, using the dorsal hand vein compliance technique, in 8 healthy male volunteers. Both noradrenaline and methoxamine produced dose-dependent venoconstriction; the geometric mean ED50 for noradrenaline was 4.15 ng min-1 and for methoxamine was 1143.54 ng min-1; the potency ratio (noradrenaline/methoxamine) was 277. Amitriptyline shifted the dose-response curve for noradrenaline to the left (ANOVA: P < 0.025; dose-ratio: 0.38) consistent with potentiation, and the dose-response curve for methoxamine to the right (ANOVA: P < 0.025; dose ratio: 2.72) consistent with antagonism. The potentiation is likely to be due to noradrenaline uptake blockade, whereas the antagonism is likely to reflect the blockade of post-junctional alpha 1-adrenoceptors.

Adolescent↗
PubMed1991

Participation by purines in the modulation of norepinephrine release by methoxamine.

The alpha 1-receptor agonist methoxamine reduced, by a prazosin sensitive mechanism, the nerve stimulation evoked release of norepinephrine in the rat caudal artery. The effect of methoxamine was also antagonized by the purinoceptor antagonist 8-(p-sulfophenyl)theophylline suggesting an involvement of endogenous purines in this process. Indeed, methoxamine caused the release of adenine nucleotides and adenosine, an action which was blocked by prazosin. These results suggest that methoxamine releases ATP or a related purine which in turn decreases transmitter release by acting on prejunctional purinoceptors.

Adenine Nucleotides↗
PubMed1987

Prostaglandin output from and the spontaneous inotropism of uterine horns isolated from underfed rats at different stages of the sex cycle. Smooth muscle contractile influences of indomethacin and of methoxamine.

The influences of a period of 15 days of restricted diet (50% of the normal food intake) in rats sacrificed at different stages of the sex cycle (proestrus, estrus, metestrus and diestrus), were explored on: (1) the magnitude of uterine spontaneous phasic contractions (isometric developed tension = IDT); (2) the release of prostaglandins (PGs) F2 alpha and E2; from the uterus and (3) the myometrial inotropic responses evoked by methoxamine and indomethacin. At estrus and at proestrus, preparations from restricted diet rats exhibited greater initial (post-isolation) IDT and better contractile constancy during 60 min than did uteri from normal fed rats. This enhanced contractile constancy, but not that of preparations from control fed rats, was prevented by incubation "in vitro" with indomethacin (10(-6) M). At metestrus and at diestrus, uteri from normal fed rats presented higher initial levels of IDT and even more sustained contractile constancy than at estrus or at proestrus. Moreover, contractile profiles remained unaltered following the dietary restriction and the presence of indomethacin evoked similar negative inotropic actions in both experimental groups (fed and underfed). Dose-response curves for methoxamine documented its positive, but different, inotropic actions in the two groups and at the four periods of the estrous cycle. Indeed, in the underfed group at estrus and at proestrus, dose-response curves for methoxamine were shifted to the left of those in fed controls, a situation prevented by indomethacin (10(-6) M); whereas at metestrus and at diestrus, no differences in the inotropic reactivity towards methoxamine between the two experimental groups, were detected. On the other hand, indomethacin shifted to the right dose-response curves for the agonist, both in preparations from normal fed and from restricted diet rats. The generation and release of PGF2 alpha and of PGE2 were explored under normal and restricted diet conditions, both at estrus and at diestrus. Following the dietary restriction, the output of PGE2 from estrous uteri was augmented in comparison to controls, whilst the release of PGF2 alpha was not affected. At diestrus, dietary restriction failed to alter the uterine output of either one of these PGs. Results suggest that a greater generation and release of PGE2, following underfeeding, appears to subserve the increased spontaneous motility and the greater sensitivity of the rat uterus for adrenoreceptor agonists.

Animals↗
PubMed1977

Acute coronary occlusion: prolonged increase in collateral flow following brief administration of nitroglycerin and methoxamine.

Regional coronary blood flow was determined with the radioactive microsphere technique 10 an 70 minutes and 2 1/2 and 5 hours after abrupt occlusion of the left anterior descending coronary artery in 12 closed chest sedated dogs. In six dogs, nitroglycerin, 200 to 400 microng/min, was infused intravenously 10 to 70 minutes after occlusion. Methoxamine was administered to return blood pressure and heart rate to prenitroglycerin levels. Ten minutes after occlusion (before treatment) collateral flow values and ischemic zone endocardial/epicardial flow ratios were equivalent in untreated (0.11+/-0.03 ml/min per g; 0.31+/-0.05) and treated dogs (0.14+/-0.02 ml/min per g; 0.29+/-0.03). In untreated dogs, collateral flow did not change over 5 hours; the endocardial/epicardial flow ratio was decreased at 5 hours (0.21+/-0.05, P less than 0.05). In contrast, in treated dogs, collateral flow and the endocardial/epicardial flow ratio were increased at 70 minutes (0.27+/-0.04 ml/min per g, P less than 0.05; 0.53+/-0.10, P less than 0.05). Most importantly, collateral flow remained elevated 5 hours after occlusion (0.26+/-0.03 ml/min per g, P less than 0.05) although treatment was discontinued 70 minutes after occlusion. Hence, collateral flow was unchanged over 5 hours of occlusion in untreated dogs, but short-term treatment with nitroglycerin and methoxamine resulted in a sustained increase in collateral flow. These findings may be a result of stimulation by nitroglycerin and methoxamine of the spontaneous rate at which intrinsic collateral function increases after ischemia. Alternatively, nitroglycerin and methoxamine may maintain cell viability until collateral vessels develop spontaneously.

Animals↗
PubMed1999

The androgenic effect of norethisterone and 5alpha-norethisterone on the contractile response of the rat vas deferens to methoxamine and serotonin.

Norethisterone (NET) and its metabolite 5alpha-norethisterone (5alpha-NET) are competitors for the androgen receptor. The sensitivity of the rat vas deferens to the contractile action of methoxamine and serotonin is regulated by hormonal and anatomical factors. The aim of this study was to evaluate the ability of NET and 5alpha-NET to induce the androgen-regulated contractile response to methoxamine and serotonin in the epididymal and prostatic portions of rat vas deferens. Adult male rats either intact, castrated or steroid-treated castrated were used. The contractility was recorded isometrically, and non-cumulative concentration-response curves to either methoxamine or serotonin were obtained. NET and 5alpha-NET partially restored the sensitivity to methoxamine and serotonin in the epididymal portion of castrated rats. The maximal responses to both agonists were significantly higher than those observed in castrated rats, and significantly lower than the responses observed in either intact or androgen-treated castrated rats. The prostatic portion was less responsive to both agonists than the epididymal portion, in all groups but castrated rats, as castration induced sensitivity to both agonists. NET and 5alpha-NET displayed a partial though similar androgenic activity in the rat vas deferens. These results contrast with previous reports where a decrease of androgenic effect due to the 5alpha-reduction of NET has been found.

Animals↗
PubMed1996

Renal response to methoxamine in portal hypertensive rats: role of prostaglandins and nitric oxide.

BACKGROUND/AIMS: In the present study we have evaluated the role of nitric oxide and prostaglandins in the renal vascular response to a vasoconstrictor (methoxamine) and to endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators. METHODS: The experiments were performed in isolated and perfused kidneys of portal vein ligated and sham rats under various treatments. RESULTS: Baseline renal perfusion pressure was lower in the portal vein ligated than in the sham group (37.2 +/- 2.6 vs 48.4 +/- 2.5 mmHg). Indomethacin (10(-5)M) did not modify baseline renal perfusion pressure in any group, but the nitric oxide inhibitor N(W)-Nitro-L-Arginine (10(-4) M) increased it in both sham and portal vein ligated kidneys, but without abolishing the differences between them. The vasoconstrictor renal response to methoxamine was blunted in portal vein ligated rats compared to controls. Indomethacin did not modify this renal hyporesponsiveness, but N(W)-Nitro-L-Arginine completely abolished it. In another set of experiments, both acetylcholine and nitroprusside caused dose-dependent vasodilation in kidneys, preconstricted with methoxamine, from sham and portal vein ligated rats, and there were no significant differences between them. N(W)-Nitro-L-Arginine reduced acetylcholine-induced vasodilation and did not modify the vasodilation evoked by nitroprusside. CONCLUSIONS: These results indicate that the renal vasculature of portal vein ligated rats shows a basal reduction in perfusion resistance that is not related to nitric oxide or prostaglandins. However, increased nitric oxide production interferes with the effects of the alfa-agonist methoxamine. This suggests that nitric oxide plays an important role in the modulation of the renal vascular responses to vasoconstrictors in portal hypertension.

Acetylcholine↗