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PubMed1981

Inhibitory effects of some catecholamines on contractions of uterine strips isolated from estrous and spayed rats. Influence of endogenous and exogenous prostaglandins on the action of methoxamine.

Cumulative dose-response curves were produced for the effect of different adrenergic agonists on the contractions of uterine strips from natural estrous and ovariectomized rats. Isoproterenol, norepinephrine and phenylephrine inhibited uterine spontaneous contractions, whilst methoxamine stimulated them. The inhibitory influences were blocked by propranolol and the excitatory effect of methoxamine was abolished by phentolamine. However, the sensitivity of the rat uterus to beta- and alpha-adrenergic agonists varied depending on the hormonal state i.e. strips from rats in natural estrus were more sensitive to inhibitory effect of beta-agonist than were those from ovariectomized animals. On the contrary, the apparent potency and the efficacy of an alpha-agonist (methoxamine) was higher in ovariectomized uterine strips than in those from estrous rats. Indomethacin, at a concentration known to inhibit the endogenous synthesis of prostaglandins, depressed the spontaneous activity of strips from spayed rats and prevented the response to methoxamine, whereas in strips from natural estrous rats, the drug was unable to modify either the spontaneous contractions or the stimulating action of methoxamine. In addition in the presence of threshold doses of PGE1, PGE2 and F2 alpha the dose-response curve to methoxamine shifted to the left for uterus from ovariectomized animals. The results suggest that uterine strips from estrous rats have more affinity to the effect of beta-adrenergic agonists, whereas those from spayed animals were more sensitive to the effect of an alpha-adrenergic agent. Also the effectiveness of an alpha-adrenergic agonist, methoxamine, appears to be related to unaltered tissue prostaglandins.

Animals↗
PubMed1987

Effects of a selective alpha 1-adrenoceptor agonist, methoxamine, on sexual behavior and penile reflexes.

Methoxamine, an adrenergic agonist with selectivity for the alpha 1-adrenoceptor, when administered intraperitoneally 10 minutes prior to mating tests (1 to 5 mg/kg), effected reductions in the ejaculatory threshold, evidenced by a decrease in the number of intromissions preceding ejaculation. In mounting tests after penile anesthetization, a test which specifically assesses sexual motivation, 3 mg/kg methoxamine was without a stimulatory effect. Further, in penile reflex tests (ex copula) 1 mg/kg methoxamine was without effect, whereas 5 mg/kg decreased the number of erections, cups and flips per test, and increased the incidence of seminal emission. These data indicate a facilitation of the ejaculatory mechanism, both in and ex copula, coupled with an inhibition of erectile responses for moderate doses of methoxamine. Treatment of male rats with the alpha 2-adrenoceptor agonist clonidine (0.25 mg/kg, IP, five minutes pretest) drastically reduced the number of animals exhibiting intromissive and ejaculatory behavior in mating tests. This suppressive effect of clonidine was not prevented by prior treatment with methoxamine (3 mg/kg, 10 minutes pretest and five minutes preclonidine). Further, ST-91, a polar analog of clonidine which does not readily enter the central nervous system, was without effect on male sexual behavior. Since (1) the effects of methoxamine administration are not of similar quality or magnitude to those reported earlier after yohimbine, an alpha 2-adrenoceptor antagonist, (2) since concurrent stimulation of alpha 1- (by methoxamine) and alpha 2- (by clonidine) adrenoceptors is followed by a suppression of sexual behavior similar to that seen after clonidine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Hypertensive effects of methoxamine on arterial mechanics in rats: analysis based on exponentially tapered T-tube model.

Methoxamine, a specific alpha1-selective adrenoceptor agonist, has proven to be useful in the treatment of hypotension, especially hypotension due to failure of the sympathetic nervous system. This study is to explore the vascular dynamic response to methoxamine in Wistar-Kyoto rats, based on the exponentially tapered T-tube model. The pulsatile aortic pressure and flow signals before and after the administration of methoxamine (0.025 mg/kg) were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively. Hemodynamic parameters, such as aortic characteristic impedance, wave transit time, and arterial load compliance, were inferred from the aortic pressure and flow signals to describe the pulsatile nature of blood flow in the vasculature. The hypertensive effects of methoxamine on the static components of ventricular afterload were characterized by (1) little change in cardiac output, (2) a decrease in heart rate and (3) an increase in aortic pressure and total peripheral resistance. As for the pulsatile components of ventricular afterload, no significant changes in aortic characteristic impedance and wave transit time were observed, suggesting that the distensibility of the aorta was not altered in rats after the administration of methoxamine. In contrast, there was a significant drop in arterial load compliance mainly due to the elevated arterial blood pressure in methoxamine-treated rats. In conclusion, methoxamine at the dose of 0.025 mg/kg has a greater effect on peripheral resistance vessels than on Winkessel vessels in the rat systemic circulation.

Adrenergic alpha-Agonists↗
PubMed1975

Stimulation of adenosine 3',5'-monophosphate formation in rat cerebral cortical slices by methoxamine: interaction with an alpha adrenergic receptor.

Methoxamine elicits a rapid accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in rat cerebral cortical slices with maximal effects at 100 muM. The accumulations of cyclic AMP elicited by this amine are completely blocked by the alpha adrenergic antagonists, phenoxybenzamine and dihydroergokryptine, partially blocked by the alpha antagonist, phentolamine, and unaffected by the beta blocking agent, propranolol, or by the local anesthetic, tetracaine. The magnitude of the accumulations of cyclic AMP elicited by methoxamine in cerebral cortical slices of four rat strains (F-344, ACI, BUF, and Sprague-Dawley) exhibit a strong negative correlation with spontaneous motor activity and a positive correlation with the magnitude of norepinephrine-elicited accumulations of cyclic AMP. The stimulatory interaction of methoxamine with alpha adrenergically regulated cyclic AMP-generating systems differs from the interaction of norepinephrine with alpha receptors as evidenced by the following observations: 1) the stimulatory effects of methoxamine and norepinephrine are nearly additive; 2) the stimulatory effects of methoxamine and adenosine are nearly additive, whereas the effects of norepinephrine and adenosine are much more than additive. Methoxamine, however, does not increase further the magnitude of accumulation of cyclic AMP elicited by a combination of norepinephrine and adenosine. The results are consonant with the interaction of methoxamine with alpha adrenergic receptors which are normally activated by norepinephrine only to a marginal extent. However, in the presence of adenosine, these receptors are now sensitive to activation by norepinephrine.

Adenosine↗
PubMed1992

The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats.

This study examined whether an increased activity of the endothelium-derived relaxing factor, nitric oxide, may account for the hyporesponsiveness to vasoconstrictors in portal hypertension. We performed dose-response curves to methoxamine, an alpha-adrenoceptor agonist, with and without N omega-nitro-L-arginine, a specific inhibitor of nitric oxide synthesis, in experimental portal hypertension. Partial portal vein-ligated or sham-operated rats were pretreated with a continuous intravenous infusion of either N omega-nitro-L-arginine (50 micrograms.kg-1.min-1) or saline. Thirty minutes after starting the infusion of N omega-nitro-L-arginine or saline an infusion of methoxamine (10, 30 and 100 micrograms.kg-1.min-1) was added. Total peripheral resistance was calculated from mean arterial pressure and cardiac index. Repeated measurements of cardiac index were performed by a thermodilution technique. In portal vein-ligated rats pretreated with saline, the increase in total peripheral resistance after methoxamine infusion was significantly less than that of sham-operated rats (0.2 +/- 0.1 vs. 1.0 +/- 0.3, 0.6 +/- 0.1 vs. 1.6 +/- 0.3 and 3.7 +/- 0.5 vs. 6.1 +/- 0.7 mm Hg.ml-1.min.100 gm, p less than 0.05, methoxamine 10, 30 and 100 micrograms.kg-1.min-1, respectively). In the presence of N omega-nitro-L-arginine, the change in total peripheral resistance after methoxamine infusion was similar in both groups (p greater than 0.05). In conclusion, this study demonstrates that a vascular hyporesponsiveness to methoxamine is present in portal vein-ligated rats and that this hyporesponsiveness is reversed by blockade of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of alpha 1-adrenoceptor stimulation with methoxamine and phenylephrine on spontaneously beating rabbit sino-atrial node cells.

Effects of methoxamine and phenylephrine on the action potential and the membrane currents in spontaneously beating rabbit sino-atrial node cells were examined by means of a two-microelectrode voltage-clamp technique. Both methoxamine and phenylephrine (10(-4) mol/l) prolonged the cycle length (CL) and the action potential duration (APD), significantly. At concentrations higher than 3 x 10(-4) mol/l, phenylephrine increased the maximum rate of rise of action potential (Vmax) but methoxamine reduced it. Both agents depolarized the maximum diastolic potential (MDP). These changes in the action potential parameters occurred in a concentration-dependent manner. In the presence of phentolamine (10(-5) mol/l), methoxamine (3 x 10(-4) mol/l) did not modify the action potential parameters. Also, phenylephrine did not affect them during exposure to phentolamine (10(-5) mol/l) and pindolol (10(-7) mol/l). In voltage-clamp experiments, at 10(-3) mol/l both methoxamine and phenylephrine slightly increased the slow inward current (Isi), but decreased the time-dependent outward current (Ik). The steady-state activation variable of Ik (p infinity) was unaffected by these agents. The hyperpolarization-activated current (Ih) was suppressed in the presence of methoxamine, but enhanced in the presence of phenylephrine. An additional application of pindolol (10(-7) mol/l) during exposure to phenylephrine (10(-3) mol/l) depressed the action potential amplitude (APA) and Vmax, and prolonged CL slightly. Under the same condition, all the membrane currents (Isi, Ik and Ih) were decreased. In addition, the time courses of decay for Isi were not modified in the absence and the presence of phenylephrine (10(-3) mol/l) and phenylephrine plus pindolol (10(-7) mol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1975

The time course of the effects of beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillary muscle.

In the isolated papillary muscle of the rabbit the time course of the effects of selective beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3',5'-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3 times 10(-7) M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10(-4) M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10(-5) M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile forced and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3 times 10(-7) M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10(-4) M) was not affected by papaverine (10(-5) M). Furthermore, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by beta-adrenoceptor stimulation, and indicate further that the stimulation of alpha-adrenoceptors evokes its positive inotropic effec through a mechanism other than that elicited by beta-adrenoceptor stimulation, i.e., independent of cAMP.

Animals↗
PubMed1996

Methoxamine-induced inhibition of the positive inotropic effect of endothelin via alpha1-adrenoceptors in the rabbit heart.

The influence of methoxamine on the positive inotropic effect of endothelin was assessed in the isolated rabbit ventricular myocardium. Methoxamine by itself elicited a positive inotropic effect and it simultaneously inhibited the positive inotropic effects of endothelin-1 and endothelin-3 without affecting the acceleration of the hydrolysis of phosphoinositide that was induced by the endothelin isopeptides. By contrast, the positive inotropic effects induced by elevation of concentration of external Ca2+ ions, by Bay k 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate), by dihydroouabain and by forskolin were unaffected by methoxamine. The inhibitory action of methoxamine was abolished by alpha1-adrenoceptor antagonists, such as prazosin, WB 4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) and (+/-)-tamsulosin; and it was inhibited to a lesser extent by chlorethylclonidine. In addition, methoxamine did not modify the specific binding of [125I]endothelin-3 to ventricular membrane fraction. These results indicate that methoxamine antagonizes the positive inotropic effect of endothelin isopeptides at the level of the signal-transduction process, subsequent to acceleration of the hydrolysis of phosphoinositide, via activation of alpha1-adrenoceptors in the rabbit ventricular myocardium.

Adrenergic alpha-Agonists↗
PubMed1987

The effect of epinephrine versus methoxamine on regional myocardial blood flow and defibrillation rates following a prolonged cardiorespiratory arrest in a swine model.

Recent studies in swine have shown that larger doses of epinephrine than those currently employed for cardiopulmonary resuscitation (CPR) significantly improve regional myocardial blood flow following prolonged cardiac arrest. The dose-response effect of a pure alpha-adrenergic agonist, methoxamine, on regional myocardial blood flow has not been investigated in this setting. This study compared the effect of high-dose epinephrine with graded doses of methoxamine on regional myocardial blood flow, oxygen delivery/utilization, and defibrillation rates during CPR. Twenty swine were instrumented for regional myocardial blood flow measurements using radiolabeled tracer microspheres. Measurements of regional myocardial blood flow, oxygen delivery, and oxygen consumption were made during normal sinus rhythm. Ventricular fibrillation was then induced. Following 10 minutes of ventricular fibrillation, CPR was initiated with a pneumatic compressor. Regional myocardial blood flow, oxygen delivery, and oxygen consumption were then measured during CPR. Following 3 minutes of CPR, the swine were allocated to one of four treatment groups (five per group): group I, epinephrine 0.2 mg/kg; group II, methoxamine 0.1 mg/kg; group III, methoxamine 1.0 mg/kg; and group IV, methoxamine 10.0 mg/kg. One minute after drug administration, regional myocardial blood flow, oxygen delivery, and oxygen consumption measurements again were made. Three and one half minutes after drug administration, defibrillation was attempted. Regional myocardial blood flow following drug administration was compared using an analysis of covariance. Epinephrine (0.2 mg/kg) significantly improved myocardial blood flow (P less than .002) for all tissues examined compared with all doses of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A comparison of epinephrine and methoxamine for resuscitation from electromechanical dissociation in human beings.

Electromechanical dissociation (EMD) is an organized electrical depolarization of the heart without synchronous myocardial fiber shortening and, therefore, without cardiac output. Patients in EMD have a poor prognosis for resuscitation and long-term survival. The beneficial effect in resuscitation of epinephrine, the adrenergic agent currently recommended, has been shown to depend on stimulation of alpha-adrenergic vasoconstriction. The beta-adrenergic inotropic and chronotropic effects of epinephrine are theoretically detrimental by increasing myocardial oxygen consumption and subendocardial ischemia. The purpose of our study was to determine whether the pure alpha agonist methoxamine was superior to epinephrine in human beings in EMD as determined by survival at one hour. These two agents were compared in a prospective, randomized, and double-blinded study involving 80 patients with EMD of various causes seen in the emergency department and internal medicine inpatient service. The advanced cardiac life support (ACLS) algorithm (current at the time of our study) for resuscitation from EMD was used, with the blinded study drug (epinephrine 1 mg or methoxamine 10 mg) administered where the algorithm calls for epinephrine. Calcium and isoproterenol also were used in the majority of cases according to ACLS standards but never prior to the use of methoxamine or epinephrine. Survival data are summarized as: survival less than one hour, 22 patients receiving methoxamine, 22 receiving epinephrine; one to six hours, 15 patients receiving methoxamine, 13 patients receiving epinephrine; six to 12 hours, one patient receiving epinephrine; more than 24 hours but not surviving to discharge, three patients receiving methoxamine, two patients receiving epinephrine; and survival to discharge, one patient receiving epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Prevention of spinal anaesthesia-induced hypotension in the elderly: i.m. methoxamine or combined hetastarch and crystalloid.

We have compared two methods of reducing hypotension during spinal anaesthesia in elderly patients, 6% hetastarch and crystalloid or methoxamine 10 mg i.m., in terms of haemodynamic stability and requirements for additional vasopressors. Sixty-two patients (aged 60-97 yr) undergoing surgical fixation of fractured neck of femur were allocated randomly to receive 6% hetastarch (Hespan) 500 ml followed by Hartmann's solution 500 ml (group HS, n = 32) or a bolus injection of methoxamine 10 mg i.m. (group MX, n = 30), 10 min before induction of spinal anaesthesia with 0.5% hyperbaric bupivacaine 2.25-3.0 ml. Arterial pressure was measured non-invasively by an oscillotonometer at 2-min intervals from 0 to 40 min and at 5-min intervals thereafter. Methoxamine 2 mg i.v. was given if systolic arterial pressure (SAP) decreased to < 100 mm Hg. Hypotension was defined as a 25% decrease from baseline SAP or mean arterial pressure (MAP). Patient data, sensory level and blood loss were similar in the two groups. SAP and MAP increased initially from baseline until induction of spinal anaesthesia and then decreased for 30 min in both groups, but remained higher in group MX (P < 0.05). Heart rate (HR) decreased from baseline in group MX (P < 0.05) and was less than in group HS at all times from 2 to 60 min (P < 0.01). The incidence of SAP hypotension (47% vs 75%; P = 0.03, odds ratio (OR) = 3.43) and MAP hypotension (47% vs 67%; P = 0.09, OR = 2.51) was less in group MX than in group HS. Requirements for rescue methoxamine i.v. (27% vs 53%, P = 0.04, OR = 3.11) was less in group MX than in group HS but the dose of rescue methoxamine given (mean 6.3 (95% confidence intervals 3.0-9.6) vs 8.9 (5.6-12.2) mg) and time to onset of hypotension (20.7 (14.5-26.7) vs 17.3 (11.4-23.1) min) were similar in groups MX and HS, respectively. We conclude that methoxamine 10 mg i.m., given 10 min before induction of spinal anaesthesia in normovolaemic elderly patients, reduced subsequent SAP and MAP hypotension, HR and requirements for rescue vasopressor therapy compared with a combination of 6% hetastarch 500 ml and crystalloid 500 ml. The previously reported benefit of such volume administration may not extend to the elderly.

Aged↗
PubMedDate not supplied

Differential interactions of clonidine and methoxamine with the postsynaptic alpha-adrenoceptor of rabbit main pulmonary artery.

We investigated the dependence upon extracellular Ca2+ of contractile responses of the isolated rabbit main pulmonary artery to the alpha-adrenoceptor subtype-selective agonists clonidine (alpha 2) and methoxamine (alpha 1). The calcium-entry blocker verapamil caused a weak, surmountable antagonism of contractile responses to methoxamine, whereas the concentration-response curve of clonidine was antagonized in a noncompetitive manner with a marked depression of maximal responses. Withdrawal of Ca2+ from the physiological saline solution virtually abolished contractile responses to clonidine, without significantly affecting methoxamine-induced responses. We, therefore, determined if clonidine and methoxamine were interacting with the same population of vascular postsynaptic alpha-adrenoceptors. We found that the alpha 1-antagonist prazosin and the alpha 2-antagonist yohimbine caused competitive blockade of contractile responses to both agonists. However, the potency of both antagonists was significantly greater against clonidine than methoxamine. This may reflect a heterogeneity in the population of postsynaptic alpha-adrenoceptors of the rabbit main pulmonary artery. On the other hand, the difference in extracellular Ca2+ sensitivity of clonidine- and methoxamine-induced contractions may be explained as a differential mode of stimulation of the postsynaptic alpha 1-adrenoceptor, possibly through separate, interacting recognition sites for both agonists.

Animals↗
PubMed1995

Effect of methoxamine on noradrenaline release in the caudal artery of hypertensive rats.

1. The effect of methoxamine, an alpha1-adrenoceptor agonist, on the overflow of endogenous noradrenaline (NA) was examined in the electrically field stimulated (EFS) caudal artery obtained from Wistar rats, Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). 2. Methoxamine inhibited the EFS-evoked release of endogenous NA in the arteries from Wistar rats and WKY, but not in the arteries of SHR. 2-chloroadenosine, a purinoceptor agonist, also inhibited the NA release in the arteries from normotensive rats but not in the arteries of SHR. 3. The inhibitory effect of methoxamine was blocked by adenosine deaminase and potentiated by adenosine uptake inhibitor, dipyridamole. 4. Methoxamine caused the release of adenine nucleotides and adenosine from the caudal arteries of WKY and SHR. 5. These suggest that the inhibitory effect of methoxamine on NA release is mediated by endogenous adenyl purines and that the failure of methoxamine to inhibit NA release in the caudal artery of SHR is due to a dysfunction of the prejunctional purinoceptors on sympathetic nerve terminals.

Adenine Nucleotides↗
PubMed1994

Regional haemodynamic responses to acetylcholine, methoxamine, salbutamol and bradykinin during lipopolysaccharide infusion in conscious rats.

1. The aim of the study was to assess the regional haemodynamic responsiveness to vasoconstrictor and vasodilator challenges during continuous 24 h infusion of lipopolysaccharide (LPS) in conscious Long Evans rats. 2. Rats were chronically instrumented for the measurement of regional haemodynamics (either internal and common carotid or renal, superior mesenteric and hindquarters) and received 3 min of infusions of acetylcholine (22 nmol min-1), methoxamine (120 nmol min-1), salbutamol (0.83 nmol min-1) and bradykinin (14.4 nmol min-1) at 2, 6 and 24 h after the start of saline or LPS (150 micrograms kg-1 h-1) infusion (rats with carotid probes received only acetylcholine and methoxamine). 3. During infusion of LPS there was a changing haemodynamic profile. After 2 h, there was a modest hypotension and vasodilatation in the internal carotid, renal and hindquarters vascular beds. After 6 h, arterial blood pressure had returned to baseline, there was still vasodilatation in the renal vascular bed but vasoconstriction in the internal and common carotids and the hindquarters. After 24 h, there was hypotension, tachycardia and generalized vasodilatation. 4. Acetylcholine caused a fall in blood pressure, tachycardia and hyperaemic vasodilatation in the carotid and renal vascular beds. Throughout the infusion of LPS, the carotid vasodilator response was enhanced after 2 h, reduced after 6 h and enhanced again after 24 h, whereas the renal vasodilator response to acetylcholine was either reduced (6 h) or absent (2 and 24 h); at this juncture the hypotensive response to acetylcholine was also enhanced and the tachycardia was reduced. 5. Methoxamine caused a rise in blood pressure, a fall in heart rate, and vasoconstriction in all the vascular beds monitored. During infusion of LPS, the pressor response to methoxamine was consistently reduced as were the vasoconstrictor responses in the carotid and mesenteric vascular beds, whereas the renal and hindquarters vasoconstrictor responses to methoxamine were only significantly reduced at some time points (renal 6 h, hindquarters 2 and 6 h).6. Salbutamol caused hypotension, tachycardia and hyperaemic vasodilatation, particularly in the hindquarters vascular bed. Throughout the infusion of LPS, the cardiovascular responses to salbutamol were substantially attenuated.7. Bradykinin caused hypotension, tachycardia and hyperaemic vasodilatation in the renal, mesenteric and hindquarters vascular beds. During the infusion of LPS, the hypotensive response to bradykinin was consistently augmented, and the tachycardia was consistently reduced, but the regional haemodynamic profile changed with time. Thus, after 2 h, the mesenteric vasodilator response was augmented and the hindquarters vasodilator response was reduced; after 6 h, the mesenteric vasodilator response appeared normal, but the renal and hindquarters vasodilator responses were reduced; after 24 h, the hindquarters vasodilator response was markedly augmented and the renal response had changed to a vasoconstriction.8. The present findings indicate marked regional variations in response to acetylcholine, methoxamine,salbutamol and bradykinin with time during LPS infusion. The changes observed are likely to reflect the interplay of a number of endogenous vasodilator and vasoconstrictor systems; further investigations will be required to clarify the mechanisms involved.

Acetylcholine↗
PubMed2003

Changes in body temperature and sleep-wakefulness after intrapreoptic injection of methoxamine in rats.

Several pieces of evidence suggest that the noradrenergic afferents in the medial preoptic area produce sleep and hypothermia by acting on alphal adrenergic receptors. On the other hand, in a few studies monitoring body temperature with a rectal probe, preoptic injection of the alphal adrenergic agonist methoxamine produced contradictory changes in body temperature and sleep-wakefulness. Such contradictions call for the re-examination of methoxamine induced body temperature changes using a better technique like telemetric recording. In the present study, we monitored body temperature and sleep-wakefulness simultaneously after the micro-injection of 0.5, 1, and 2 micromol methoxamine, into the medial preoptic area of adult male Wistar rats. Methoxamine injection produced hypothermia but no major change in sleep-wakefulness during the 3 hours after drug injection, except for a short period (15 min) of sleep after 120 min of injection. A short period of wakefulness, coinciding with the maximum fall in body temperature (30 min after injection) occurred when methoxamine was administered at higher doses. The results of this study indicate that alphal adrenergic receptors participate in preoptically mediated thermoregulatory measures that reduce body temperature. Hypothermia induced by methoxamine might have masked the hypnogenic action of this drug.

Adrenergic alpha-Agonists↗
PubMed1976

Actions of methoxamine and tryptamine and their interactions with cyproheptadine and phenoxybenzamine on cat spinal cord segmental reflexes.

The effects of norepinephrine, methoxamine and tryptamine were assessed on the monosynaptic and polysynaptic segmental reflexes in the unanesthetized, decerebrated acute spinal cat. Their selectivity of action was determined by studying the interactions of methoxamine and tryptamine with two antagonists, cyproheptadine and phenoxybenzamine. Potentials were evoked by stimulating either the L7 or S1 dorsal root and were recorded from the corresponding ipsilateral ventral root. Norepinephrine did not affect reflex activity, whereas methoxamine facilitated both the monosynaptic and polysynaptic potentials in a dose-related manner when infused over 20 minutes. Tryptamine facilitated both the monosynaptic and polysynaptic reflex potentials. This increase was dose related for the monosynaptic reflex but not for the polysynaptic reflex. Phenoxybenzamine blocked the facilitatory effects of methoxamine and did not antagonize the effects of tryptamine on the segmental reflex. The facilitatory effects of tryptamine were effectively blocked by cyproheptadine. Cyproheptadine failed to reduce the polysynaptic response to methoxamine, although it partially antagonized the monosynaptic facilitation. These findings demonstrate that methoxamine and tryptamine facilitate the segmental reflex by different modes of action and provide additional evidence for noradrenergic and tryptaminergic systems in the spinal cord.

Animals↗
PubMed1997

The Y1 antagonist BIBP 3226 inhibits potentiation of methoxamine-induced vasoconstriction by neuropeptide Y.

We investigated the interaction of neuropeptide Y (NPY) with the alpha 1-adrenoceptor agonist, methoxamine, in control of mean arterial pressure, renovascular resistance and mesenteric vascular resistance in anaesthetized rats. Infusion of 3.0 but not 0.3 microgram/kg/min NPY enhanced the elevations of all three haemodynamic parameters caused by bolus injections of methoxamine (10-100 micrograms/kg). These enhancements largely involved a prolongation of the methoxamine effects. While infusion of the Y1 NPY receptor-selective antagonist, BIBP 3226 (10 micrograms/kg/min), alone did not alter methoxamine-induced vasoconstriction, it inhibited the potentiation by NPY. We conclude that NPY can potentiate methoxamine-induced vasoconstriction in vivo. This is mediated predominantly, if not exclusively, via the Y1 receptor. Endogenously released NPY does not appear to reach sufficient concentrations to cause tonic systemic vasoconstriction or potentiation thereof in the anaesthetized rat.

Animals↗
PubMed1988

Methoxamine is an effective unconditioned stimulus for cardiovascular conditioning.

New Zealand albino rabbits received classical conditioning training in which a 35-sec tone conditioned stimulus was paired with a bolus injection of methoxamine hydrochloride (Vasoxyl), an alpha 1-adrenergic agonist. Heart rate (HR) and blood pressure (BP) responses were recorded. Methoxamine produced a precipitous rise in BP and bradycardia as an unconditioned response (UR); pairings of tone and methoxamine over a 5-day period resulted in a gradually appearing tachycardia conditioned response (CR) which occurred shortly following tone onset. On the other hand, the BP CR was a pressor response. Accordingly, the HR CR was opposite in direction and, thus, apparently compensatory to the UR, whereas the BP CR was similar in direction to the UR. Neither of these cardiovascular changes were observed in control animals receiving either unpaired presentations of tone and methoxamine or tones paired with physiological saline. Most animals receiving either paired or unpaired infusions of methoxamine also showed consistent elevations in baseline HR as training progressed, relative to their respective day 1 levels, thus suggesting the development of compensatory HR CRs to the contextual cues associated with training.

Acoustic Stimulation↗