Cardiac Renin

Danser, A. H., van Kats, J. P., Admiraal, P. J., et al. 1994. Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis. Hypertension 24 37 18. 

Booz, G.W., Day, J.N.E., and Baker, K.M. 2002. Interplay between the cardiac renin angiotensin system and JAK-STAT signaling Role in cardiac hypertrophy, ischemia/reperfusion dysfunction, and heart failure. J. Mol. Cell. Cardiol. 34 1443-1453. 

Edward D. Frohlich, Richard N. Re The Local Cardiac Renin Angiotensin-Aldosterone System. 2005 ISBN 0-387-27825-7... 

Xiang, W Kong, J., Chen, S Cao, L.P., Qiao, G Zheng, W Liu, W Li, X., Gardner, D.G. and Li, Y.C. (2005) Cardiac hypertrophy in vitamin D receptor knockout mice role of the systemic and cardiac renin-angiotensin systems. American Journal of Physiology. 

Glonidine. Clonidine decreases blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance. It activates central a2 adrenoceptors ia the brainstem vasomotor center and produces a prolonged hypotensive response. Clonidine, most efficaciously used concomitantly with a diuretic in long-term treatment, decreases renin and aldosterone secretion. 

In some patients with hypertension and in all patients with cardiac failure, the renin-angiotensin system is activated to an undesired degree, burdening the heart. The consequences of diminished ANG II generation by ACE inhibitors are multiple. In patients with hypertension, blood pressure is reduced as a result... 

Urata H, Kinoshita A, Misono KS, Bumpus FM. Husain A Identification of a highly specific chy-mase as the major angiotensin Il-forming enzyme in the human heart. J Biol Chem 1990 265 22348. Silver RB, Reid AC, Mackins CJ, Askwith T, Schaefer U, Herzlinger D, Levi R Mast cells a unique source of renin. Proc Natl Acad Sci USA 2004 101 13607. Mackins CJ, Kano S, Sevedi N, Schafer U, Reid AC, Machida T, Silver RB, Levi R Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. J Clin Invest 2006 116 1063. 

P-blocker therapy was ineffective in preventing coronary heart disease, cardiovascular mortality, and all-cause mortality when compared to diuretics for elderly patients (60 years of age or greater) treated for primary hypertension. Clearly, the effects of P-blockers on blood pressure are complex and difficult to ascribe to one or two mechanisms. Rather, the varied effects of negative chronotropic and inotropic properties along with reduced renin levels (Fig. 2-3) appear to result in an overall reduction in cardiac output and/or reduction in peripheral resistance. 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

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. 

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. 

Nesiritide is manufactured using recombinant techniques and is identical to the endogenous B-type natriuretic peptide secreted by the ventricular myocardium in response to volume overload. Consequently, nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation increases in cardiac output natriuresis and diuresis and decreased cardiac filling pressures, sympathetic nervous system activity, and renin-angiotensin-aldosterone system activity. 

The exact hypotensive mechanism of /1-blockers is not known but may involve decreased cardiac output through negative chronotropic and inotropic effects on the heart and inhibition of renin release from the kidney. 

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. 

Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in increased sympathetic outflow from the vasomotor center, producing an increase in heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic. 

Minoxidil is a more potent vasodilator than hydralazine, and the compensatory increases in heart rate, cardiac output, renin release, and sodium retention are more dramatic. Severe sodium and water retention may precipitate congestive heart failure. Minoxidil also causes reversible hyper-... 

Oxdralazine (67) is characterized by a bis(2-hydroxyethyl)amino group attached to position 6 of 3-hydrazinopyridazine. The antihypertensive effect of (67) has been studied in rats (spontaneous, desoxycorticosteron-induced, and renal hypertension) [223]. Its effect in the long-term treatment of hypertensive rats on plasma and kidney renin activities has been reported [224]. The effects of (67) on the general and cardiac haemodynamics of anaesthe-... 

The novel endocrine glands are the skin, gastrointestinal tract, adipose tissue, kidney (juxtaglomerular apparatus in the cortex which secretes renin that indirectly controls aldosterone secretion, via angiotensin-11), pineal gland, which secretes melatonin, and the heart (cardiac myocytes in the atria, which secrete atrial natriuretic peptide). 

Counter-regulation in acute hypotension due to vasodilators (B). Increased sympathetic drive raises heart rate (reflex tachycardia) and cardiac output and thus helps to elevate blood pressure. Patients experience palpitations. Activation of the renin-angioten-sin-aidosterone (RAA) system serves to increase blood volume, hence cardiac output. Fluid retention leads to an increase in body weight and, possibly, edemas. These counter-regulatory processes are susceptible to pharmacological inhibition ( 3-blockers, ACE inhibitors, ATI-antagonists, diuretics). 

Their efficacy in many illnesses is explained by the competitive binding of )3-adrenore-ceptors in the autonomic nervous system by basically any of the employed drags of the l-aryloxy-3-aminopropanol-2 class, which result in reduction of heart rate and strength of cardiac beats, slowing of atrioventricular conductivity, reduction of the level of renin in the plasma, and reduction of blood pressure. The main effects of 8-adrenoblockers are expressed at the level of the vasomotor center in the hypothalamus, which result in a slowing of the release of sympathetic, tonic impulses. Included in the main group of... 

Propranolol lowers blood pressure in the majority of patients with essential hypertension. These effects can be caused by a number of possible mechanisms, including lowering cardiac output, inhibiting the release of renin, lowering sympathetic release from the central nervous system, inhibiting the release of norepinephrine from sympathetic postganglionic nerves, and others. 

The secretion of renin itself is controlled by the nervous system, and possibly by a recently discovered cardiac peptide hormone. 

Moreover, whether or not hypertension is caused by an elevated level of renin or other reasons, angiotensin-converting enzyme inhibitors lower both systolic and diastolic arterial pressure in hypertensive patients, and their effects are enhanced by diuretics. Angiotensin-converting drugs of this series (captopril, enalapril) are effective antihypertensive drugs used both independently and in combination with other drugs to treat all types of hypertension as well as to treat cardiac insufficiency. 

Reduction in plasma volume secondary to the enhanced excretion of sodium ions and water and the regression of edema, if present. These effects are accompanied by a reduction in cardiac preload. During long-term treatment most of these effects are counteracted by various regulatory mechanisms, such as a persistent rise in plasma renin and aldosterone. 

These potent diuretic agents interact with almost the entire nephron, including Henle s loop (Fig. 7). Their primary effect is probably the inhibition of the active reabsorption of chloride ions, which then leads to the enhanced excretion of sodium ions and water. Plasma volume is reduced as a result of these effects, whereas in the long-term both cardiac preload and afterload will diminish. The metabolic side-effects of the loop diuretics are globally the same as those of the thiazides, with some incidental differences. Plasma renin activity increases by loop diuretic treatment and it can be well imagined that this effect is noxious in the long-term management of heart failure. The loop diuretics provoke a clearly... 

Phenoxybenzamine and phentolamine, in addition to blocking postsynaptic a-receptors, also block aj-receptors on nerves and therefore can enhance the release of norepinephrine. When norepinephrine exerts a postsynaptic action by means of -adrenoceptors (e.g., cardiac stimulation, renin release), blockade of presy-naptic a2-receptors by phenoxybenzamine and phentolamine may actually potentiate the responses. Prazosin blocks responses mediated by postsynaptic aj-receptors but has no effect on the presynaptic a2-receptors. Thus,... 

The actions of p-blockers on blood pressure are complex. After acute administration, blood pressure is only slightly altered. This is because of the compensatory reflex increase in peripheral vascular resistance that results from a (3-blocker-induced decrease in cardiac output. Vasoconstriction is mediated by a-receptors, and a-receptors are not antagonized by (3-receptor blocking agents. Chronic administration of (3-blockers, however, results in a reduction of blood pressure, and this is the reason for their use in primary hypertension (see Chapter 20). The mechanism of this effect is not well understood, but it may include such actions as a reduction in renin release, antagonism of (3-receptors in the central nervous system, or antagonism of presynaptic facilita-tory (3-receptors on sympathetic nerves. 

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