Adrenergic receptors cardiac

Adrenergic receptor agonists, in particular clen-buterol, have been used for their hypertrophic effects on skeletal and also cardiac muscle. They can increase muscle growth in cattle (illegal in many countries) but have also been used by body-builders and athletes as anabolic dtugs. 

Relatively selective stimulation of Pi-adrenergic receptors can be achieved with dobutamine. This is a racemic drug of which both isomers activate the Pi-receptor, and in addition the (-) isomer activates ( -receptors whereas the (+) isomer activates p2-receptors the simultaneous activation of ai- and p2-receptors results in no major net effect on peripheral resistance, and thus the overall cardiovascular effects are mediated by Pi-stimulation leading to increases in cardiac contractility and output. Dobutamine is used for the short-term treatment of acute cardiac failure and for diagnostic purposes in stress echocardiography. 

Inflammatory cytokines have been implicated in the pathophysiology of HF.9 Several proinflammatory (e.g., tumor necrosis factor-a [TNF-a], interleukin-1, interleukin-6, and interferon-y) and anti-inflammatory cytokines (e.g., interleukin-10) are overexpressed in the failing heart. The most is known about TNF-a, a pleiotrophic cytokine that acts as a negative inotrope, stimulates cardiac cell apoptosis, uncouples 3-adrenergic receptors from adenylyl cyclase, and is related to cardiac cachexia. The exact role of cytokines and inflammation in HF pathophysiology continues to be studied. 

Low-dose dopamine is not without adverse reactions and most studies have failed to evaluate its potential toxicities. Adverse reactions that may be associated with low-dose dopamine include tachycardia, arrhythmias, myocardial ischemia, depressed respiratory drive, and gut ischemia. Low-dose dopamine has also been postulated to impair resistance to infection through a reduction in prolactin concentrations.21 Furthermore, significant overlap in receptor activation occurs. Therefore, doses considered to activate only dopamine receptors may increase cardiac output and blood pressure through dopamine s effect on 3- or a-adrenergic receptors. 

Sympathetic nerve activity causes an increase in blood pressure through many mechanisms, including an increase in cardiac activity and vasoconstriction. Activation of the sympathetic system also causes the stimulation of Pi-adrenergic receptors on the renin-producing cells, which promotes renin release. 

Because cardiac muscle is myogenic, nervous stimulation is not necessary to elicit the heart beat. However, the heart rate is modulated by input from the autonomic nervous system. The sympathetic and parasympathetic systems innervate the SA node. Sympathetic stimulation causes an increase in heart rate or an increased number of beats/min. Norepinephrine, which stimulates ( -adrenergic receptors, increases the rate of pacemaker depolarization by increasing the permeability to Na+ and Ca++ ions. If the heart beat is generated more rapidly, then the result is more beats per minute. 

Lefkowitz, R. J., Haber, E., and O Hara, D. (1972). Identification of the cardiac beta-adrenergic receptor protein Solubilization and purification by affinity chromatography. Proc. Natl. Acad. Sci. USA 69, 2828-2832. 

Of the many types of adrenergic receptors found throughout the body, which is most likely responsible for the cardiac stimulation that is observed following an intravenous injection of epinephrine ... 

The answer is e. (Hardman, p 215 J Ritodrine hydrochloride is a selective [ -adrenergic agonist that relaxes uterine smooth muscle. It also has the other effects attributable to J3-adrenergic receptor stimulants, such as b rone hod il at ion, cardiac stimulation, enhanced renin secretion, and hyperglycemia. 

The answer is b. (Katzung, p 166.) Propranol nonspecifically blocks pj-adrenergic receptors. It lowers blood pressure primarily by decreasing cardiac output... 

Clonidine, guanabenz, guanfacine, and methyldopa lower BP primarily by stimulating a2-adrenergic receptors in the brain, which reduces sympathetic outflow from the vasomotor center and increases vagal tone. Stimulation of presynaptic oq-receptors peripherally may contribute to the reduction in sympathetic tone. Consequently, there may be decreases in heart rate, cardiac output, total peripheral resistance, plasma renin activity, and baroreceptor reflexes. 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

Prazosin volume, thereby reduces cardiac output Alpha-adrenergic receptor antagonist, inhibits symphathetic... 

Atenolol stimulation of arteriolar contraction Beta-adrenergic receptor anatagonist, reduces cardiac output... 

The inotropic effects of these agents are not mediated via direct stimulation of -adrenergic receptors or indirectly by release of catecholamines, but by selective inhibition of cardiac cAMP phosphodiesterase (PDE) type III [25,35-40]. Recently, it has been demonstrated that the imidazole core is primarily responsible for PDE isozyme specificity, whereas the dihydropyri-dazinone moiety is responsible for inhibitory potency the phenylene moiety obviously acts mainly as a spacer [26]. A five-point model for positive inotropic activity of PDE III inhibitors has been elaborated [41]. 

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