Arterioles sympathetic nerves effect

O -Adrenoceptor antagonists (o -blockers) are competitive inhibitors at the level of Q -adrenoceptors. These receptors are found in many organs and tissues, but their predominant functional importance is to mediate the vasoconstrictor effects of endogenous catecholamines (noradrenaline, adrenaline) released from the sympathetic nerve endings. Conversely, Q -adrenoceptor antagonism by means of an a-blocker will inhibit this constrictor activity and hence cause vasodilatation. This vasodilator effect occurs in both resistance vessels (arterioles) and capacitance vessels (veins), since a-adrenoceptors are present in both types of vascular structures. Accordingly, both cardiac afterload and preload will be lowered, in particular when elevated. 

Methyldopa (L-ar-methyl-3,4-dihydroxyphenylalanine) is an analog of L-dopa and is converted to a -methyldopamine and -methylnorepinephrine this pathway directly parallels the synthesis of norepinephrine from dopa illustrated in Figure 6-5. Alpha-methylnorepinephrine is stored in adrenergic nerve vesicles, where it stoichiometrically replaces norepinephrine, and is released by nerve stimulation to interact with postsynaptic adrenoceptors. However, this replacement of norepinephrine by a false transmitter in peripheral neurons is not responsible for methyldopa s antihypertensive effect, because the cr-methylnorepinephrine released is an effective agonist at the a -adrenoceptors that mediate peripheral sympathetic constriction of arterioles and venules. Direct electrical stimulation of sympathetic nerves in methyldopa-treated animals produces sympathetic responses similar to those observed in untreated animals. 

Dopamine has been used for several decades for the treatment of human patients with oliguric ARF (Denton et al 1996, Dishart Kellum 2000). A constant low-dose i.v. infusion (0.5 to 3.0(jLg/ kg/min) produces a dose-dependent increase in the RBF and increases the excretion of sodium and water. Some studies have also reported increases in the GFR but this response is less consistent. A dose-dependent increase in the RBF has also been documented in normal horses (Trim et al 1989). Low doses of dopamine augment the RBF primarily by inducing renal arteriolar vasodilatation by stimulating dopamine D receptors in the intrarenal blood vessels. This effect is typically greater in afferent than in efferent glomemlar arterioles and is the mechanism by which dopamine may also promote an increase in the GFR. A secondary role is the stimulation of D2 receptors on presynaptic sympathetic nerve terminals, which inhibits norepinephrine release. Intermediate doses... 

Hydralazine (apresoline) causes direct relaxation of arteriolar smooth muscle, possibly secondary to a fall in intracellular Ca concentrations. The drug does not dilate epicardial coronary arteries or relax venous smooth muscle. Hydralazine-induced vasodilation is associated with powerful stimulation of the sympathetic nervous system, likely due to baroreceptor-mediated reflexes, which results in increased heart rate and contractility, increased plasma renin activity, and fluid retention all of these effects counteract the antihypertensive effect of hydralazine. Although most of the sympathetic activity is due to a baroreceptor-mediated reflex, hydralazine may stimulate NE release from sympathetic nerve terminals and augment myocardial contractility directly. Most of hydralazine s effects are confined to the cardiovascular system the decrease in blood pressure after administration is associated with a selective decrease in vascular resistance in the coronary, cerebral, and renal circulations, with a smaller effect in skin and muscle. Because of preferential dilation of arterioles, postural hypotension is not common, and hydralazine lowers blood pressure equally in the supine and upright positions. 

They examined the adrenaline-like effect of a large number of compounds, and they found, on the whole, that approximation to adrenaline in the chemical structure is linked with an increase and a sharper specificity of the action. Barger and Dale introduced the term sympathomimetic, which means that the effects produced resemble those obtained by stimulation of the so-called sympathetic system of nerves. The study of the sympathomimetic amines represents one of the earliest and most successful attempts to correlate pharmacological action with chemical structure. The sympathomimetic action includes rise of arterial blood pressure, stimulation of the heart muscle, constriction of the arterioles and either stimulation or inhibition of smooth muscle. Some of the drugs also stimulate the central nervous system. 

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