Effects of some catecholamines on the cat cardiovascular system: interactions with adrenoceptor antagonists
Insights
This study reveals that beta 1-receptors in cat vasculature cause vasodilation, alongside beta 2-receptors. Cardiostimulant beta 2-receptors also exist in the cat heart, complicating catecholamine action interpretation.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Adrenergic Receptor Research
Background:
- Catecholamines like norepinephrine and epinephrine exert diverse cardiovascular effects.
- These effects are mediated through interactions with alpha and beta-adrenergic receptors.
- The specific roles of beta-1 and beta-2 adrenergic receptors in feline cardiovascular regulation are not fully elucidated.
Purpose of the Study:
- To investigate the roles of alpha and beta-adrenergic receptors in mediating cardiovascular responses to various catecholamines in cats.
- To differentiate the vascular and cardiac effects of selective beta-1 and beta-2 adrenergic receptor stimulation and blockade.
- To explore the presence and function of beta-1 mediated vasodilation and beta-2 mediated cardiac stimulation in feline cardiovascular systems.
Main Methods:
- Intravenous administration of catecholamines (norepinephrine, epinephrine, isoproterenol, N-t-butylnorepinephrine, oxymethyleneisoproterenol, RO363) in anesthetized cats.
- Assessment of hemodynamic parameters: heart rate, mean arterial blood pressure, cardiac output, total peripheral resistance, and stroke volume.
- Administration of adrenergic receptor antagonists (phentolamine, propranolol, atenolol, butoxamine) to identify receptor subtypes involved.
Main Results:
- Pressor responses to norepinephrine and epinephrine were primarily alpha-receptor mediated via increased peripheral resistance.
- Beta-1 receptor blockade (atenolol) abolished dilator responses to norepinephrine and beta-1 selective agonists (oxymethyleneisoproterenol, RO363).
- Beta-2 receptor blockade (butoxamine) abolished dilator responses to epinephrine, N-t-butylnorepinephrine, and isoproterenol, indicating beta-1 vasodilation and beta-2 vasodilation.
- Atenolol showed agonist-dependent inhibition of cardiac responses, suggesting cardiostimulant beta-2 receptors in the feline heart.
- Butoxamine did not exhibit significant agonist-dependent inhibition of cardiac responses.
Conclusions:
- The feline vasculature possesses beta-1 receptors that mediate vasodilation, in addition to beta-2 receptors.
- The feline heart contains cardiostimulant beta-2 receptors.
- The complex interplay of mixed beta-adrenoceptor populations in the feline cardiovascular system complicates the interpretation of catecholamine actions.
Abstract:
The effects of intravenous infusions of norepinephrine, epinephrine, isoproterenol, N-t-butylnorepinephrine, oxymethyleneisoproterenol, and RO363 on heart rate, mean arterial blood pressure, cardiac output, total peripheral resistance, and stroke volume were evaluated in chloralose-anaesthetized cats before and after phentolamine, propranolol, atenolol, and butoxamine. Pressor responses to both norepinephrine and epinephrine largely resulted from alpha-receptor-mediated increases in total peripheral resistance. Vasomotor reversal was noted with both drugs in the presence of alpha-receptor blockade. Dilator responses to norepinephrine were abolished by the beta 1-receptor selective antagonist atenolol, as were those to the beta 1-receptor selective agonists oxymethyleneisoproterenol and RO363. Dilator responses to epinephrine were abolished by the beta 2-receptor selective antagonist butoxamine, as were those to N-t-butylnorepinephrine (beta 2-selective) and isoproterenol (nonselective). These results indicate that in addition to beta 2-receptors, beta 1-receptors subserving vasodilatation occur in the cat vasculature. Atenolol displayed agonist-dependent inhibition of the cardiac responses. Responses to noradrenaline, RO363, and oxymethyleneisoproterenol were blocked to a greater extent than were those to epinephrine, N-t-butylnorepinephrine, and isoproterenol. Butoxamine did not display any marked agonist-dependent inhibition of cardiac responses. Nevertheless, the results are in accord with previous suggestions that cardiostimulant beta 2-receptors exist in the cat heart. Interpretation of the actions of catecholamines may be complicated by mixed beta-adrenoceptor populations in the cat cardiovascular system.
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