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PubMed1986

Prophylactic action of hexamethonium, trimethaphan, and mecamylamine against diisopropyl fluorophosphate poisoning in mice.

Prophylactic Action of Hexamethonium, Trimethaphan, and Mecamylamine against Diisopropyl Fluorophosphate Poisoning in Mice. Chiou, G. C. Y., Chang, W. T. S., and Aimoto, T. (1986). Fund. Appl. Toxicol. 6, 35-43. Hexamethonium, trimethaphan, and mecamylamine are ganglionic blockers which can reduce acetylcholine (ACh) release presynaptically. All these agents are capable of protecting mice from diisopropyl fluorophosphate (DFP) intoxication by prolonging the latent period of death or by completely preventing death. Combinations of these agents with 2-pyridine aldoxime methochloride (2-PAM) (50 mg/kg) improved prophylactic action even further. These results indicate that reduction of ACh release presynaptically plus neutralization of organophosphates with 2-PAM could be an effective way to reduce mortality in patients exposed to organophosphorus poisons.

Animals↗
PubMed2002

The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the mu-opioid receptor.

Wild-type and mu-opioid receptor knockout (MORKO) mice were used to investigate the role of corticosterone (CORT) and the mu-opioid receptor (MOR) in chronic morphine-mediated immunosuppression. We found that although plasma CORT concentrations in CORT infusion (10 mg/kg/day) and morphine-pellet implantation (75 mg) mice were similar (400-450 ng/ml), chronic morphine treatment resulted in a significantly higher (two- to threefold) inhibition of thymic, splenic, and lymph node cellularity; inhibition of thymic-lymphocyte proliferation; inhibition of IL-2 synthesis; and activation of macrophage nitric oxide (NO) production when compared with CORT infusion. In addition, results show that the inhibition of IFN-gamma synthesis and splenic- and lymph node-lymphocyte proliferation and activation of macrophage TNF-alpha and IL-1beta synthesis occurred only with chronic morphine treatment but not with CORT infusion. These morphine effects were abolished in MORKO mice. The role of the sympathetic nervous system on morphine-mediated effects was investigated by using the ganglionic blocker chlorisondamine. Our results show that chlorisondamine was able to only partially reverse morphine's inhibitory effects. The results clearly show that morphine-induced immunosuppression is mediated by the MOR and that although some functions are amplified in the presence of CORT or sympathetic activation, the inhibition of IFN-gamma synthesis and activation of macrophage-cytokine synthesis is CORT-independent and only partially dependent on sympathetic activation.

Animals↗
PubMed2002

Effects of antihypertensive drugs on ultrasound production and cardiovascular responses in 15-day-old rats.

When exposed to extreme cold or injected with the alpha(2)-adrenoceptor agonist, clonidine, infant rats emit ultrasonic vocalizations (USVs). Based upon the cardiovascular changes that accompany these two manipulations, especially decreased venous return, it was hypothesized that USVs are the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that increases venous return. If this hypothesis is correct, then other anithypertensive drugs that decrease venous return should evoke USVs. In Experiment 1, sodium nitroprusside (SNP, 400 microg/kg), a direct-acting dilator of arteries and veins, was administered to 15-day-old rats under thermoneutral conditions while cardiac rate and ultrasound production were monitored. In Experiment 2, femoral artery pressure was monitored after SNP administration. Infants responded to SNP administration with decreased arterial pressure and tachycardia and, in addition, significantly increased ultrasound production. In Experiment 3, chlorisondamine (5 mg/kg), a ganglionic blocker that causes vasodilation and bradycardia, and hydralazine (20 mg/kg), a selective dilator of arteries, was administered to 15-day-olds. As predicted, chlorisondamine evoked ultrasound production and hydralazine did not. These results introduce SNP and chlorisondamine as only the second and third known agents capable of independently evoking USVs in thermoneutral conditions, and provide further support for the notion that ultrasound production is triggered by decreased venous return.

Aging↗
PubMed1995

Metabolic and hormone-related responses to caffeine in rats.

The time course of effects of caffeine on plasma glucose and non-esterified fatty acids (NEFA) were measured and related to various hormonal responses associated with substrate mobilization and utilization. Participation of the sympatho-adrenal system (SAS) in the metabolic and hormonal actions of caffeine was also investigated by the use of ganglionic blockade. Following 50 mg kg-1 i.p. injections of caffeine in rats, plasma glucose increased 25% and NEFA 40%, and these actions were parallelled by an elevation of plasma insulin, ACTH and corticosterone, without changes in glucagon. It is suggested that the insulin response is related to the plasma glucose increase and possibly also to an action of cAMP. When caffeine was injected in rats previously treated with the ganglionic blocker, hexamethonium, none of the responses mentioned above were modified. These results show that the glucose and NEFA responses are independent of glucagon secretion and are due not only to SAS activation but also to other mechanisms such as the increased ACTH and corticosterone secretion. It is also suggested that the mobilization of substrates by caffeine is mediated, through these various mechanisms, by the activation of cAMP and by phosphodiesterase inhibition.

Adrenocorticotropic Hormone↗
PubMed2003

Mechanisms involved in the pressor response to noradrenaline injection into the cingulate cortex of unanesthetized rats.

The cingulate cortex (CC) is involved in cardiovascular modulation. CC electrical or chemical stimulation may evoke either pressor or depressor responses, depending on the stimulated site and experimental conditions such as anesthesia. Noradrenaline (NA) is involved in cardiovascular regulation and it is present throughout the cortex. However, there is no report on the cardiovascular effects of intracortical injections of NA. We attempted to verify the effect of NA injection into the CC and to identify possible receptor and peripheral mechanisms involved. NA injection caused pressor responses accompanied by bradycardia, in unanesthetized rats. These responses were markedly reduced under urethane anesthesia. The pressor response was blocked by intracortical pretreatment with phenoxybenzamine or the selective alpha(1)-antagonist WB4101, and it was not affected by pretreatment with the selective alpha(2)-antagonist RX821002, suggesting that alpha(1)-adrenoceptors mediate the response. The pressor response was potentiated by pretreatment with the ganglion blocker mecamylamine and it was abolished by pretreatment with the vasopressin antagonist, dTyr(CH(2)) (5)(Me)AVP or by hypophysectomy. Circulating vasopressin levels were increased after NA injection into the CC. The present results indicate that the pressor response to local injection of NA within the CC is independent of sympathetic nerve activation and is mediated by vasopressin release.

Adrenergic alpha-Antagonists↗
PubMed1988

Role of primary sensory neurons in the central effects of nicotine.

Utilizing single unit recording techniques the nicotine-induced excitation of noradrenaline (NA)-containing neurons in the locus coeruleus (LC) was analyzed. Low doses of nicotine (40-160 micrograms, IV) were found to dose-dependently increase the LC firing rate. The effect was antagonized by pretreatment with the quaternary ganglionic blockers hexamethonium (12 mg/kg, IP) and chlorisondamine (0.3 mg/kg, IV). Also, neonatal treatment with capsaicin, a procedure that is associated with a selective degeneration of primary sensory C-fibre afferents, clearly antagonized the effect of nicotine on LC neurons. The typical effect of nicotine on LC discharge was, in all essentials, mimicked by the quaternary nicotinic agonist tetramethylammonium (TMA). We here propose that the action of nicotine on central NA neurons is primarily executed peripherally via activation of primary sensory C-fibre afferents.

Animals↗
PubMed1999

Cigarette smoke aggravates experimental colitis in rats.

BACKGROUND & AIMS: Tobacco smoking has a complex effect on intestinal inflammation, being protective in ulcerative colitis, whereas it aggravates Crohn's disease. The beneficial effect of smoking has been attributed to nicotine, but the mechanisms underlying the adverse effect are still under investigation. The aim of this study was to examine the effect of cigarette smoking on experimental colitis in rats and to investigate the underlying mechanism. METHODS: Rats were exposed daily to cigarette smoke by means of a specialized smoking chamber. Control rats were placed in the same chamber without introducing smoke. In parallel experiments, rats received the ganglionic blocker hexamethonium before smoke exposure. After 2 weeks, colitis was induced by dinitrobenzenesulfonic acid (DNBS), and inflammation was assessed 3 days later. RESULTS: Exposure to cigarette smoke significantly increased macroscopic and histological damages as well as myeloperoxidase activity compared with sham-treated controls. Treatment with hexamethonium before smoking reversed the effect of the smoke on the colitis, improving all parameters. CONCLUSIONS: Exposure to cigarette smoke aggravates DNBS-induced colitis in the rat. This effect is reversed by hexamethonium, suggesting that a neural pathway is involved.

Animals↗
PubMed1989

Spinovagal reflex modulation of gastric motility in response to mucosal nociceptive stimulation in the anaesthetized rat.

In anesthetized rats treated with guanethidine, the pylorus was ligated. A catheter was inserted into the stomach via the mouth and anchored by a ligature around the cervical oesophagus. The catheter was used for instillation into the stomach of a fixed volume (9 ml) of either isotonic or 1 M NaCl and for the recording of intragastric pressure. Neurogenic modulation of gastric motility caused by either solution was analysed by studying the effect of the systemic administration of the ganglionic blocker hexamethonium on gastric tone and on phasic motor activity. Gastric motility was not significantly changed by hexamethonium in the animals that had been subjected to isotonic NaCl. After intragastric treatment with 1 M NaCl, however, hexamethonium caused increased gastric tone and decreased phasic motor activity. An analysis of these results suggests that 1 M NaCl activated vagal non-adrenergic, non-cholinergic relaxatory and cholinergic excitatory motor neurons, respectively. These chemically induced modulations of gastric motility were dependent on the spinal cord and, most probably, were due to activation of the mucosal sensory endings of the splanchnic nerves, leading to reflex spinovagal motor adjustments.

Animals↗
PubMed1997

Rat amylin mediates a pressor response in the anaesthetised rat: implications for the association between hypertension and diabetes mellitus.

Amylin (or islet amyloid polypeptide) has been reported to have binding sites in the central nervous system and the kidney and has been shown to activate plasma renin. It has been postulated that this peptide may be an important mechanistic link between hypertension and diabetes in the insulin resistance syndrome. To explore this issue, the effects of rat amylin on mean arterial blood pressure were investigated in anaesthetised rats. Amylin elicited a pressor response of approximately 10 mmHg (maximal at 100 pmol.kg-1) which was apparent within 30-60 s and persisted over 15 min. At higher concentrations amylin elicited a hypotensive response (negative log IC50 8.52 mol.kg-1). The novel amylin receptor antagonist AC413 (12 nmol.kg-1.min-1) reduced the pressor response but not the hypotensive effects of amylin. The peptide antagonist calcitonin gene-related peptide (CGRP)8-37 (12 nmol.kg-1.min-1) reduced the pressor response elicited by amylin and also antagonized the hypotensive effect of amylin. Pre-treatment of animals with the ganglion blocker mecamylamine (3 mg.kg-1 s.c.) reduced the pressor effect of amylin. Following the administration of the angiotensin converting enzyme inhibitor ramiprilat (300 nmol.kg-1 i.v.) the pressor response to amylin was reduced. Salmon calcitonin also elevated blood pressure in the anaesthetised rat; doses of amylin and salmon calcitonin associated with a pressor effect were associated with increases in plasma renin activity. We conclude that amylin may act centrally to elevate blood pressure in the anaesthetised rat, possibly through activation of the renin angiotensin system.

Amino Acid Sequence↗
PubMed1976

Hypotensive and antiarrhythmic effects of a new alkaloid, the 13-hydroxylupanine-2-pyrrolcarbonic acid ester, from the Madagascan plant Cadia ellisiana.

The alkaloid 13-hydroxylupanine-2-pyrrolcarbonic acid ester (Hoe 933) from the Madagascan plant Cadia ellisiana has an hypotensive and antiarrhythmic effect. The hypotensive effect in dogs, monkeys, and rats anaesthetized with barbiturates reaches its maximum with 0.2 mg/kg i.v. However, the hypotensive effect is much weaker in conscious animals. The enteral absorption in the dog is good; an intraduodenal dose of only 0.5 mg/kg lowered the blood pressure. In the isolated rabbit heart whose accelerator nerves were intact, the perfusion with concentrations of 0.6 mug/min Hoe 933 (total dose 6 mug) decreased the release of norepinephrine from the nerve endings, reduced the positive inotropic effect, and diminished the increase in heart rate produced by electrical stimulation of the accelerator nerve. The effect of the stimulation of the accelerator nerve on dp/dt in dogs in situ was considerably diminished by such low doses as 10 and 25 mug/kg i.v. Consequently, the alkaloid inhibits sympathetic impulse transmission. Sympathetic circulatory reflexes are weakened by the compound. The alkaloid has also a ganglionic blocking effect, which is demonstrated on the upper cervical ganglion of the cat. The effect of preganglionic stimulation of the nictitating membrane was reduced with 200 mug Hoe 933/kg i.v. In the isolated guinea pig heart the effect of nicotine on heart rate and contraction was diminished. In this respect the ganglion blocker pentolinium is 8 times more active. The antifibrillatory effect of Hoe 933 was demonstrated with 0.3 mg/kg i.v. in supercooled cats, the antiarrhythmic activity was evident with 0.5 mg/kg i.v. in dogs intoxicated with K-strophanthin. In isolated hearts of guinea pigs, a dose of only 6 mug/heart inhibited ventricular fibrillation induced by aconitine and digitoxin. Even the toxicity of digoxin was diminished by previous administration of 300 mug/kg i.v. The relative refractory period and the duration of the action potential were prolonged in the isolated papillary muscle of the guinea pig heart.

Alkaloids↗
PubMed2005

Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats.

After periods of microgravity or bed rest, individuals often exhibit reduced Vo(2 max), hypovolemia, cardiac and vascular effects, and autonomic dysfunction. Recently, alterations in expression of vascular and central nervous system NO synthase (NOS) have been observed in hindlimb-unloaded (HU) rats, a model used to simulate physiological effects of microgravity or bed rest. We examined the effects of 14 days of hindlimb unloading on hemodynamic responses to systemic NOS inhibition in conscious control and HU rats. Because differences in NO and autonomic regulation might occur after hindlimb unloading, we also evaluated potential differences in resting autonomic tone and effects of NOS inhibition after autonomic blockade. Administration of nitro-L-arginine methyl ester (L-NAME; 20 mg/kg iv) increased mean arterial pressure (MAP) to similar levels in control and HU rats. However, the change in MAP in response to L-NAME was less in HU rats, that had an elevated baseline MAP. In separate experiments, atropine (1 mg/kg iv) increased heart rate (HR) in control but not HU rats. Subsequent administration of the ganglionic blocker hexamethonium (30 mg/kg iv) decreased MAP and HR to a greater extent in HU rats. Administration of L-NAME after autonomic blockade increased MAP in both groups to a greater extent compared with intact conditions. However, the pressor response to L-NAME was still reduced in HU rats. These data suggest that hindlimb unloading in rats reduces peripheral NO as well as cardiac parasympathetic tone. Along with elevations in sympathetic tone, these effects likely contribute to alterations in vascular control and changes in autonomic reflex function following spaceflight or bed rest.

Animals↗
PubMed2002

Cardiovascular and behavioural components of conditioned fear to context after ganglionic and alpha-adrenergic blockade.

This study investigates the contribution of the peripheral nervous system to the cardiovascular component of long lasting (40 min) conditioned fear responses to context. The conditioned fear response evoked by reexposure to a footshock chamber was tested 10 min after intravenous injection of either the nicotinic ganglion blocker chlorisondamine (0.6 mg/kg) or the alpha-adrenoceptor antagonist phentolamine (10 mg/kg) in six rats implanted with telemetric probes. Compared to saline controls, chlorisondamine did not change the behavioural component of the response (freezing, ultrasonic vocalizations) but almost completely abolished its cardiovascular component (mean arterial pressure and heart rate). Phentolamine also abolished the pressor response but increased the cardiac response, and ultrasonic vocalizations were reduced by half. The results indicate that the long lasting pressor response of conditioned fear to context is sympathetically mediated like the much shorter pressor response of conditioned fear to a discrete stimulus.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

[Balanced regional anesthesia based on epidural blockade in extensive abdominal interventions in aged patients].

A high risk of hemodynamic disorders is the main problem associated with regional blocking in elderly patients subjected to abdominal surgery. There are theoretical reasons for ganglionic blocking without hypotonus as a means preventing hemodynamic complications of regional anesthesia in traumatic interventions. Extensive operations on the abdominal organs were performed in 40 patients aged 60 to 82 years. Before surgery the epidural space at the levels from T12 to T7, depending on the level of the intervention, was catheterized. Epidural blocking was combined with drugs for intravenous anesthesia (dipidolor, diazepam, nitrogen oxide). Pentamine in a dose of 1.36 +/- 0.06 mg/kg/h and dopamine in a dose of 3 to 4 micrograms/kg/h were special component of anesthesia. Intubation of the trachea and forced ventilation of the lungs were used; myorelaxants were administered only before intubation. The intra- and postoperative periods were characterized by hemodynamic and metabolic stability and early postoperative rehabilitation. The authors consider that preventive ganglionic blocking without hypotonus attained by a combination of a dosed injection of a ganglion blocker and injection of a highly selective adrenomimetic dopamine in the microcirculation dose ensure the hemodynamic and metabolic stability of balanced anesthesia based on epidural blocking in elderly and senile patients subjected to extensive abdominal interventions. The proposed method of balanced anesthesia is an effective means of neurovegetative inhibition during epidural blocking as the basic component of anesthesia, which permits minimizing the doses of general anesthetics and ensures positive changes in the respiratory system of elderly patients, manifesting by improved pulmonary and bronchial conduction and improvement of blood gas composition.

Abdomen↗
PubMed2002

Rapid elevation of plasma interleukin-6 by morphine is dependent on autonomic stimulation of adrenal gland.

Several studies have demonstrated that opioids regulate a number of immune cell functions either through direct mechanisms or through the modulation of central nervous system outputs. It has been previously shown that morphine increases serum interleukin-6 (IL-6) levels; however, the mechanism by which this effect is produced is unknown. In the present study, experiments were designed to address the potential role of central opioid receptors, peripheral autonomic ganglia, and activation of the adrenals in the elevation of plasma IL-6 after morphine administration. A rapid and significant (2-fold) increase in plasma IL-6 was observed after morphine administration (10 mg/kg s.c.) to rats. This effect of morphine peaked within 30 min and remained elevated for at least 2 h. Central microinjection of morphine (10 microg/2 microl i.c.v.) mimicked the effects of peripherally administered morphine and was completely blocked by naltrexone (10 mg/kg s.c.) pretreatment. Pretreatment with a ganglionic blocker, chlorisondamine (0.5 mg/kg i.p.), also blocked the elevation of IL-6 by morphine, suggesting a role of the autonomic nervous system. In adrenalectomized animals, morphine administration did not increase IL-6 levels, whereas in adrenal demedullated animals, the effect of morphine remained intact. Thus, the adrenal cortex may be a potential source of IL-6, because IL-6 mRNA has been localized in the adrenal gland. Collectively, these data suggest a unique mechanism by which stimulation of central opioid receptors results in the elevation of plasma IL-6 through autonomic activation specifically of the adrenal cortex.

Adrenal Glands↗
PubMed2003

Influence of plasma insulin levels on antinatriuretic and vasoconstrictor actions of angiotensin-II.

The objective of the present study is to investigate whether plasma insulin levels play a role in the antinatriuretic and vasoconstrictor actions of angiotensin-II (Ang-II). We evaluated antinatriuretic function of endogenous Ang-II using an AT1 receptor antagonist, candesartan in anesthetized Sprague-Dawley rats. In control rats, candesartan produced significant increases in natriuresis and diuresis and these effects were abolished in streptozocin (STZ, 55 mg/kg i.p.) treated rats. Replacement of insulin restored these renal effects of candesartan. In a separate group of rats pretreated with an autonomic ganglionic blocker, pressor responses to Ang-II and norepinephrine (NE) before or after L-NNA, a nitric oxide synthase inhibitor were not affected by STZ treatment. However, insulin replacement greatly augmented these responses. These data provide evidence in vivo showing that insulin can enhance both antinatriuretic and vasoconstrictor actions of Ang-II. Hence exaggerated renal and vascular effects of Ang-II in the obese Zucker rats observed in our previous studies may be related to hyperinsulimemia and this phenomena could contribute to salt-sensitivity and development of sustained hypertension.

Angiotensin II↗
PubMed1999

Role of nitric oxide in the cerebral circulation during hypotension after hemorrhage, ganglionic blockade and diazoxide in awake goats.

The role of nitric oxide in cerebrovascular response to hypotension was analyzed by evaluating the changes in cerebrovascular resistance after inhibition of nitric oxide synthesis with Nw-nitro-L-arginine methyl ester (L-NAME) during three types of hypotension in conscious goats. Blood flow to one brain hemisphere was electromagnetically measured, hypotension was induced by controlled bleeding, and by i.v. administration of hexametonium (ganglionic blocker) or of diazoxide (vasodilator drug), and L-NAME was injected by i.v. route (35 mg kg-1). Under control conditions (13 goats), L-NAME increased arterial pressure from 98 +/- 3 to 123 +/- 4 mmHg and decreased cerebral blood flow from 65 +/- 3 to 40 +/- 3 ml min-1 (all P < 0.001); cerebrovascular resistance increased from 1.52 +/- 0.04 to 3.09 +/- 0.013 mmHg ml-1 min-1 (P < 0.01) (delta = 1.59 +/- 0.12 mmHg ml-1 min-1). After bleeding (five goats), mean arterial pressure decreased to 60 +/- 4 mmHg and cerebral blood flow decreased to 37 +/- 4 ml min-1 (all P < 0.01); cerebrovascular resistance did not change (1.56 +/- 0.14 vs. 1.54 +/- 0.12 mmHg ml-1 min-1, P > 0.05). During this hypotension, L-NAME increased arterial pressure to reach the normotensive values an did not affect the hypotensive values for cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 2.91 +/- 0.19 mmHg ml-1 min-1 (P < 0.01) (delta = 1.37 +/- 0.16 mmHg ml-1 min-1), and this increment is comparable to that under control conditions (P > 0.05). Ganglionic blockade (six goats) decreased arterial pressure to 67 +/- 2 mmHg) and did not affect significantly cerebral blood flow; cerebrovascular resistance decreased from 1.71 +/- 0.11 to 1.05 +/- 0.09 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 103 +/- 6 mmHg (P < 0.001), and did not affect cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 1.68 +/- 0.18 mmHg ml-1 min-1 (P < 0.01) (delta = 0.63 +/- 0.10 mmHg ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Diazoxide (six goats) decreased arterial pressure to 69 +/- 5 mmHg (P < 0.01) without changing cerebral blood flow; cerebrovascular resistance decreased from 1.89 +/- 0.11 to 1.16 +/- 0.14 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 87 +/- 6 mmHg (P < 0.05) and did not affect the hypotensive values for cerebral blood flow (P > 0.05); cerebrovascular resistance increased from the hypotensive values to 1.53 +/- 0.13 mmHg ml-1 min-1 (P < 0.05) (delta = 0.36 +/- 0.06 mmHg-1 ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Therefore, the role of nitric oxide in cerebrovascular response to hypotension may differ in each type of hypotension, as this role during hemorrhagic hypotension may not change and during hypotension by ganglionic blockade or diazoxide may decrease. These differences may be related to changes in nitric oxide release as stimuli on the endothelium (shear stress and sympathetic activity) may vary in each type of hypotension.

Animals↗
PubMed1997

Correlation between vasodilatation and secretion in the lacrimal gland elicited by stimulation of the cornea and facial nerve root of the cat.

PURPOSE: To determine whether reflex vasodilatation can be elicited in the cat lacrimal gland by electrical stimulation of the cornea, whether the vasodilatation elicited by electrical stimulation of the facial nerve root found to be the efferent arm of the cornea-lacrimal gland reflex pathway correlates with the evoked secretion in the lacrimal gland, and what kind of receptors and which autonomic ganglia are involved in lacrimal vasodilator and secretory responses. METHODS: Electrical stimulation of the cornea or facial nerve root was used to evoke a blood flow increase in the lacrimal gland and tear secretion of the urethane-chloralose-anesthetized, paralyzed, and cervically sympathectomized cat. RESULTS: The lacrimal vasodilator response depended on stimulus intensity and frequency and correlated well with the tear secretion. Injection of 2% lidocaine solution into the retrobulbar area, where the pterygopalatine ganglion is located, abolished the vasodilator and the secretory responses. Pretreatment with hexamethonium (an autonomic ganglion blocker) greatly attenuated the secretory response, even at a low dose (1 mg/kg given intravenously), although at this dose, the vasodilator response was only slightly affected. Neither phentolamine (an alpha-adrenoceptor antagonist) nor propranolol (a beta-adrenoceptor antagonist), nor a vasoactive intestinal peptide antagonist had any effect on the vasodilator or secretory responses. Scopolamine (a muscarinic receptor antagonist), although having no effect on vasodilatation, had a profound inhibitory effect on the secretory response. CONCLUSIONS: These results suggest that whereas the vasodilator and secretory responses in the lacrimal gland were well correlated, they were mediated by different mechanisms.

Adrenergic alpha-Antagonists↗
PubMed2005

Increased counteracting effect of eNOS and nNOS on an alpha1-adrenergic rise in total peripheral vascular resistance in spontaneous hypertensive rats.

OBJECTIVE: The hypertension in spontaneous hypertensive rats (SHR) may result from a hyperactive sympathetic nervous system or from insufficient bioactive nitric oxide (NO) due to increased oxidative stress. The present investigation aimed to elucidate the balance between these two systems by studying the ability of NO to oppose an adrenergic rise in total peripheral vascular resistance (TPVR). METHODS: In anesthetized, open-chest SHR and normotensive controls (WKY) on a respirator, blood pressure was recorded in the femoral artery and cardiac output measured by ascending aorta flow. Tyramine infusion (15 min, intravenously) was used to stimulate neuronal noradrenaline release. RESULTS: Tyramine induced an immediate but transient increase in TPVR, which was 4.5 times greater in SHR. After the non-selective NO synthase (NOS) inhibitor (L-NAME: N(omega)-nitro-L-arginine methyl ester), DeltaTPVRimm was 8.6 and 5.3 times increased in SHR and WKY, respectively, and TPVR remained elevated throughout the infusion period. Addition of alpha1-adrenoceptor antagonist (prazosin+L-NAME) abolished the TPVR response to tyramine. Neuronal NOS inhibitor (7-introindazole) increased DeltaTPVRimm only in SHR (2.1 times), and TPVR remained elevated. Inducible NOS inhibitor (1400W), free radical scavenger (tempol), NAD(P)H oxidase inhibitor (apocynin), angiotensin AT1 receptor antagonist (losartan), and ganglion blocker (hexamethonium) had no effect on the tyramine TPVR response in either strain. DeltaTPVR to hexamethonium, prazosin, and L-NAME were greater in SHR than WKY, and hexamethonium reduced DeltaTPVR to L-NAME in SHR only. CONCLUSIONS: The alpha1-adrenoceptor TPVR response to endogenous noradrenaline release was increased in SHR. This was not due to reduced bioavailable NO; on the contrary, NO counteraction was greatly increased, derived from endothelial NOS, with an additional role of neuronal NOS not seen in WKY. An influence of oxidative stress on these responses was not detected in either strain. In addition, a central eNOS sympathoinhibitory component appeared to influence baseline TPVR in SHR.

Adrenergic Uptake Inhibitors↗