Sympathetic nervous system cardiac effects

In addition to cardiac tissue, leptin receptors have also been identified in both cerebral and coronary vessels (Bjorbaek et al. 1997 Knudson et al. 2005). With respect to the latter it was proposed that OBR-mediated leptin-induced vasodilation occurs through an NO-dependent process and which was abolished by hyperleptinemia. This finding emphasizes the potential dual role of leptin on vascular tissue, a direct NO-dependent vasodilation and vasoconstriction occurring secondarily to central stimulation of the sympathetic nervous system. These effects will be discussed below in greater detail. 

Figure 15.5 Effects of sympathetic and parasympathetic nervous activity on mean arterial pressure. The parasympathetic nervous system innervates the heart and therefore influences heart rate and cardiac output. The sympathetic nervous system innervates the heart and veins and thus influences cardiac output. This system also innervates the arterioles and therefore influences total peripheral resistance. The resulting changes in cardiac output and total peripheral resistance regulate mean arterial pressure.

Loss of plasma volume leads to a decrease in MAP. Baroreceptors located in the aortic and carotid sinuses detect this fall in MAP and elicit reflex responses that include an increase in the overall activity of the sympathetic nervous system. Sympathetic stimulation of the heart and blood vessels leads to an increase in cardiac output (CO) and increased total peripheral resistance (TPR). These adjustments, which increase MAP, are responsible for the short-term regulation of blood pressure. Although increases in CO and TPR are effective in temporary maintenance of MAP and blood flow to the vital organs, these activities cannot persist indefinitely. Ultimately, plasma volume must be returned to normal (see Table 19.1). 

Noradrenaline and adrenaline are the classic catecholamines and neurotransmitters in the sympathetic nervous system. Noradrenaline stimulates the following subtypes of adrenoceptors P, a, U2. It has positive inotropic and chronotropic activities as a result of /3i-receptor stimulation. In addition, it is a potent vasoconstrictor agent as a result of the stimulation of both subtypes (ai,a2) of a-adrenoceptors. After intravenous infusion, its effects develop within a few minutes, and these actions disappear within 1-2 minutes after stopping the infusion. It may be used in conditions of acute hypotension and shock, especially in patients with very low vascular resistance. It is also frequently used as a vasoconstrictor, added to local anaesthetics. Adrenaline stimulates the following subtypes of adrenoceptors /3i, P2, oil, 0L2. Its pharmacological profile greatly resembles that of noradrenaline (see above), as well as its potential applications in shock and hypotension. Like noradrenaline, its onset and duration of action are very short, as a result of rapid inactivation in vivo. Both noradrenaline and adrenaline may be used for cardiac stimulation. Their vasoconstrictor activity should be kept in mind. A problem associated with the use of /3-adrenoceptor stimulants is the tachyphylaxis of their effects, explained by the /3-adrenoceptor downregulation, which is characteristic for heart failure. 

E. The effect of ganglionic blockade depends upon the predominant autonomic tone exerted within various organ systems. Since the activity of the parasympathetic nervous system predominates in the eye, the effect of ganglionic blockade is mydriasis, not miosis. Similarly, stimulation of the genital tract and urinary retention would be decreased. Since sympathetic nervous system activity predominates in blood vessels and the ventricles, vasodilation and a decreased cardiac output would follow ganglionic blockade. 

The net effects of bretylium on the electrical and mechanical properties of the heart are a composite of the direct actions of the drug on cardiac tissues and indirect actions mediated through the drug s effects on the sympathetic nervous system. 

Thus, it seems that the lack of sympathetic nervous system inhibition produced by the vasodilators, which is advantageous in some ways, can also be a disadvantage in that reflex increases in sympathetic nerve activity will lead to hemodynamic changes that reduce the effectiveness of the drugs. Therefore, the vasodilators are generally inadequate as the sole therapy for hypertension. However, many of the factors that limit the usefulness of the vasodilators can be obviated when they are administered in combination with a -adrenoceptor antagonist, such as propranolol, and a diuretic. Propranolol reduces the cardiac stimulation that occurs in response to increases in sympathetic nervous activity, and the... 

Hydralazine is generally reserved for moderately hypertensive ambulatory patients whose blood pressure is not well controlled either by diuretics or by drugs that interfere with the sympathetic nervous system. It is almost always administered in combination with a diuretic (to prevent Na+ retention) and a p-blocker, such as propranolol (to attenuate the effects of reflex cardiac stimulation and hyperreninemia). The triple combination of a diuretic, -blocker, and hydralazine constitutes a unique hemodynamic approach to the treatment of hypertension, since three of the chief determinants of blood pressure are affected cardiac output (p-blocker). 

In patients with coronary insufficiency, a -blocker can be given in conjunction with diazoxide to decrease the cardiac work associated with reflex increases in sympathetic stimulation of the heart. However, 3-blockers potentiate the hypotensive effect of diazoxide, and therefore, the dose of the vasodilator should be lowered. The dose of diazoxide should also be lowered if the patient has recently been treated with guanethidine or another drug that depresses the action of the sympathetic nervous system. Such drugs permit a greater hypotensive effect because they reduce the increase in cardiac output that normally partially counteracts the fall in pressure. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

In addition to its effects on cardiac contractility, digitalis has a direct inhibitory effect on sympathetic nervous system activity.37,60 This effect is beneficial because it decreases stress on the failing heart by decreasing excessive sympathetic stimulation of the heart and peripheral vasculature2. Therapeutic levels of digitalis likewise stabilize heart rate and slow impulse conduc-... 

Ephedrine occurs in white, rosette, or needle crystals, or as an unctuous mass. It is soluble in water, alcohol, chloroform, ether, and in liquid petrolatum, the latter solution being turbid if the ephedrine is not dry. Ephedrine melts between 34 and 40°C, depending upon the amount of water it contains it contains not more than 0.1% of ash its solutions are alkaline to litmus it readily forms salts with acids and it responds to the usual tests for alkaloids. Ephedrine excites the sympathetic nervous system, depressing smooth and cardiac muscle action, and produces effects similar to those of epinephrine. It produces a rather long-lasting rise of blood pressure and mydriasis and diminishes hyperemia. The alkaloid may be used in 0.5 to 2% oil spray. 

When injected intravenously, kinins produce a rapid fall in blood pressure that is due to their arteriolar vasodilator action. The hypotensive response to bradykinin is of very brief duration. Intravenous infusions of the peptide fail to produce a sustained decrease in blood pressure prolonged hypotension can only be produced by progressively increasing the rate of infusion. The rapid reversibility of the hypotensive response to kinins is due primarily to reflex increases in heart rate, myocardial contractility, and cardiac output. In some species, bradykinin produces a biphasic change in blood pressure—an initial hypotensive response followed by an increase above the preinjection level. The increase in blood pressure may be due to a reflex activation of the sympathetic nervous system, but under some conditions, bradykinin can directly release catecholamines from the adrenal medulla and stimulate sympathetic ganglia. Bradykinin also increases blood pressure when injected into the central nervous system, but the physiologic significance of this effect is not clear, since it is unlikely that kinins cross the blood-brain barrier. 

The randomized controlled clinical trials performed by Freis and his colleagues at the Veterans Administration Hospitals have provided some of the first solid evidence that moderate permanent hypertension has an improved prognosis when actively treated by sodium depletion (hydrochlorothiazide), by interruption of the sympathetic nervous system (reserpine) and with a vasodilator (hydralazine) (262). In parallel, the beneficial effects of this triple therapy were demonstrated in spontaneously hypertensive rats by the spectacular prevention and cure of their cardiac, vascular, and renal lesions (263). 

All the clinically available (J-blockers are competitive antagonists. Nonselective [3-blockers act at both (3 and (32 receptors, whereas car-dioselective ( -antagonists primarily block 3i receptors. These drugs also differ in intrinsic sympathomimetic activity, in central nervous system (CNS) effects, and in pharmacokinetics (Figure 7.5). Although all (3-blockers lower blood pressure in hypertension, they do not induce postural hypotension because the a-adrenoceptors remain functional therefore, normal sympathetic control of the vasculature is maintained. P-blockers are also effective in treating angina, cardiac arrhythmias,... 

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