ABSTRACT
Experiments on anesthetized rats carried out with a high-frequency ultrasonic system and tropicamide, a highly selective blocker of M4 cholinoreceptors, showed that the vasodilator effects observed after selective blockade of M4 cholinoreceptors are not organ-specific. Intravenous tropicamide (0.1 µg/kg body weight) transiently decreased systemic BP, elevated the linear and volume fl ow rates, and diminished vascular resistance in common carotid, superior mesenteric, and femoral arteries. At the same time, in most rats (76%) the fl ow rate in the portal vein did not change, while in 25% rats it insignificantly and temporarily increased. The hypothesis on possible involvement of M4 cholinoreceptor structures in cholinergic vasoconstriction is discussed.
Subject(s)
Brain/blood supply , Hindlimb/blood supply , Receptor, Muscarinic M4/antagonists & inhibitors , Splanchnic Circulation/drug effects , Tropicamide/pharmacology , Animals , Blood Flow Velocity/drug effects , Blood Pressure/drug effects , Carotid Arteries/physiology , Femoral Artery/physiology , Male , Mesenteric Artery, Superior/physiology , Muscarinic Antagonists/pharmacology , Rats , Rats, Wistar , Vascular Resistance/drug effects , Vasodilator Agents/pharmacologyABSTRACT
In experiments on rats using high frequency ultrasonic measurement technique and selective M4-cholinoreceptor antagonist tropicamide it was shown that i/v injection of the cholinolitic block agent in large doses exceeding of its selective threshold (1 mg/kg) causes pronounced inhibition of the cardiovascular system in rats. Severe transitory hypotension and bradycardia are developed, general vascular resistance, minute cardiac output, are decreased. The block of M4-cholinoreceptors with smaller doses of tropicamide (0.1-0.001 mg/kg) causes transitory dose-depended effect on hemodynamic--system blood pressure and vascular resistance, pulse, minute cardiac output, as soon as velocity of aortic blood flow, strike cardiac output are increased on the contrary. The following decrease the dose of the high selective M4-cholinolitic antagonist (0.0001 mg/kg) reveals that its negative chronotropic effect are not detected practically but tropicamide vessel action (decrease of system blood pressure and vascular resistance) are preserved distinctly. The obtained data are discussed in aspect of the possible involvement of M4-muscarinic receptor subtype in acetylcholine-induced vasoconstriction in rats.
Subject(s)
Receptor, Muscarinic M4/antagonists & inhibitors , Vasoconstriction/drug effects , Acetylcholine/pharmacology , Animals , Blood Pressure , Bradycardia/chemically induced , Cardiac Output , Cardiovascular System/drug effects , Dose-Response Relationship, Drug , Hypotension/chemically induced , Male , Muscarinic Antagonists/pharmacology , Pulse , Rats , Rats, Wistar , Receptor, Muscarinic M4/agonists , Tropicamide/pharmacology , Vascular ResistanceABSTRACT
The experiments employing high-frequency ultrasonic technique and selective blockers of M1, M3, and M4 muscarinic cholinergic receptors pirenzepine, 4-DAMP, and tropicamide, respectively, revealed individual roles of these receptors in the development of severe posthemorrhagic hypotension in rats with low or high individual resistance to circulatory hypoxia. The study showed that M1 and M4 muscarinic receptors are involved in shock-limiting and shock-activating processes, respectively, while M3 receptors exert no effect on the course of posthemorrhagic abnormalities in systemic and hepatic portal circulation and on the posthemorrhagic lifespan. Poor resistance of the cardiovascular system to circulatory hypoxia during shock development is considered to be dysregulatory pathology.
Subject(s)
Blood Circulation/physiology , Hemorrhage/complications , Hypotension/etiology , Muscarinic Antagonists/pharmacology , Receptor, Muscarinic M1/physiology , Receptor, Muscarinic M3/physiology , Receptor, Muscarinic M4/physiology , Animals , Blood Pressure/drug effects , Hypotension/physiopathology , Male , Piperidines , Pirenzepine , Rats , Rats, Wistar , Receptor, Muscarinic M1/antagonists & inhibitors , Receptor, Muscarinic M3/antagonists & inhibitors , Receptor, Muscarinic M4/antagonists & inhibitors , TropicamideABSTRACT
Ultrasound studies showed that selective antagonist of central M1 muscarinic cholinergic receptors pirenzepine (50 mg/kg intravenously) causes transitory hypotension and respiratory depression in anesthetized intact rats. The M1 receptor antagonist had no effect on cardiac output and portal blood flow. Pretreatment with pirenzepine increased the sensitivity of rats with acute massive hemorrhage to circulatory hypoxia. After blockade of central M1 muscarinic cholinergic receptors, the posthemorrhagic period was characterized by primary decompensation of blood pressure, portal blood flow, and respiration and development of low cardiac output syndrome. The animals died over the first minutes after bleeding arrest. Our results indicate that central M1 muscarinic cholinergic receptors act as shock-limiting cholinergic structures under conditions of posthemorrhagic changes in systemic and portal blood flow, as well as during respiratory dysfunction.
Subject(s)
Cardiovascular System/drug effects , Hemorrhage/complications , Muscarinic Antagonists/pharmacology , Pirenzepine/pharmacology , Receptors, Muscarinic/metabolism , Respiratory Physiological Phenomena/drug effects , Animals , Male , Rats , Rats, Wistar , Time FactorsABSTRACT
Experiments employing ultrasound technique showed that nonselective blockade of central muscarinic cholinoceptors with amizyl significantly increases the number and lifespan of rats highly resistant to acute massive blood loss. This pretreatment increased individual resistance of the circulatory system to posthemorrhagic hypoxia (blood pressure and portal blood flow rate). Preliminary blockade of central nicotinic cholinoceptors and peripheral muscarinic cholinoceptors with cyclodol and methacin, respectively, had no effect on the percentage of rats highly and low resistant to acute blood loss. Preliminary blockade of peripheral muscarinic cholinoceptors with methacin prevented the decrease in the cardiac output in low resistant animals during the posthemorrhagic period.
