Renin and

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 normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

Levi and Silver s groups [28] have shown that mast cells are an additional source of renin and constitute a unique extrarenal renin-angiotensin system they found... 

The kidneys are located on the posterior part of the abdomen on either side of the spine, below the diaphragm, and behind the liver and stomach. They are bean-shaped and weigh approximately 150 grams (0.33 lb) each. The primary function of the kidneys is excretion. They work to excrete waste products through a series of steps involving glomerular filtration, secretion, and reabsorption. The kidneys also have several endocrine (e.g., production of erythropoietin and renin) and metabolic (e.g., vitamin D activation and drug metabolism) functions. 

An efficient route for the synthesis of the Phe-Phe hydroxyethy-lene dipeptide isostere precursors utilized for the design of potential inhibitors of renin and HIV-protease was developed. The key step is the zinc-mediated stereoselective allylation of A-protected a-amino aldehydes in aqueous solution (Eq. 8.32).70 NaBF4/M (M = Zn or Sn) showed facilitating allylation of a variety of carbonyl compounds in water, and a-and y-addition products of crotylations could be alternatively obtained under the control of this novel mediator (Eq. 8.33).71... 

F5. Findling, J. W., Waters, V. O., and Raff, H The dissociation of renin and aldosterone during critical illness. J. Clin. Endocrinol. Metab. 64, 592-595 (1987). 

Limited data on occupationally exposed men indicate that the effect of lead on blood pressure may be mediated in part through the renin-angiotensin system, as evidenced by lead-related increases in plasma renin and angiotensin I levels (Campbell et al. 1985) and the kallikrein-kinin system, as indicated by a correlation between renin and kallikrein (Boscolo et al. 1981). Evidence from patients with essential hypertension and renal impairment suggests that excessive lead absorption may be involved in the development of both conditions (Batuman et al. 1983). 

Victery W, Vander AJ, Markel LK, et al. 1982a. Lead exposure begun in utero decreases renin and angiotensin II in adult rats. Proc Soc Exp Biol Med 170 63-67. 

Sympathetic stimulation of adrenergic receptors on the granular cells of the juxtaglomerular apparatus promotes secretion of renin and, consequently, formation of angiotensin II. Angiotensin II then causes ... 

Therefore, inhibition of ANP release leads to vasoconstriction and increased MAP. Furthermore, less ANP promotes the release of renin and secretion of aldosterone, which further enhance sodium reabsorption. 

Formed by sequential enzymatic cleavage by renin and then peptidyl dipeptidase (kinase 11)... 

More specific laboratory tests are used to diagnose secondary hypertension. These include plasma norepinephrine and urinary metanephrine levels for pheochromocytoma, plasma and urinary aldosterone levels for primary aldosteronism, and plasma renin activity, captopril stimulation test, renal vein renins, and renal artery angiography for renovascular disease. 

Although a high level of plasma renin appears to identify a subject likely to respond to (3-blockers the relationship between the reduction in renin level and fall in blood pressure is still obscure. While some investigators claim good correlations between the reduction in renin and blood pressure others find no such correlation (20). In fact, Stokes et al (34) showed that pindolol was able to maintain the fall in blood pressure produced by chronic administration of propranolol without maintaining the reduction in renin. 

AA 2 Families of endopeptidases (including pepsin, renin and some cathepsins in family Al) and several other families Asp Two lobes from separate genes... 

Potent inhibitor of add proteases, including pepsin, renin and cathepsin D and many microbial aspartic proteases... 

The positions of hydrolysis of the peptide bond of angiotensinogen by renin and angiotensin-1 by the converting enzyme are shown in Eigure 22.14. 

Renin [2] is an aspartate proteinase (see p. 176). It is formed by the kidneys as a precursor (prorenin), which is proteolytically activated into renin and released into the blood. In the blood plasma, renin acts on angiotensinogen, a plasma glycoprotein in... 

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. 

In therapeutic doses, hydralazine produces little effect on nonvascular smooth muscle or on the heart. Its pharmacological actions are largely confined to vascular smooth muscle and occur predominantly on the arterial side of the circulation venous capacitance is much less affected. Because cardiovascular reflexes and venous capacitance are not affected by hydralazine, postural hypotension is not a clinical concern. Hydralazine treatment does, however, result in an increase in cardiac output. This action is brought about by the combined effects of a reflex increase in sympathetic stimulation of the heart, an increase in plasma renin, and salt and water retention. These effects limit the hypotensive usefulness of hydralazine to such an extent that it is rarely used alone. 

L A. By blocking renal prostaglandin synthesis, COX-2 inhibitors, such as rofecoxib, decrease the blood flow to the juxtaglomerular apparatus, thus stimulating the release of renin and subsequent Na" retention and blood pressure elevation. Rofecoxib is neither metabolized nor induced by CYP2C9. It decreases rather than increases renal blood flow and does not increase the excretion of hydrochlorothiazide. Item D is incorrect because rofecoxib has very little effect on COX-1 and prostaglandins are not a major controlling factor of peripheral vascular tone. Rofecoxib does not decrease basal metabolic rate. 

Because adrenergic agents such as P-blockers find such extensive use as hypotensive drugs, the etiology and drug combination treatment of hypertension are of considerable interest. A discussion in any detail of this complex and confusing field goes beyond the scope of this book, however. Other aspects of hypertension will be discussed in connection with the renin and vasopressin systems and calcium channel blockers. 

Renin, angiotensin, and aldosterone play important roles in at least some people with essential hypertension. Approximately 20% of patients with essential hypertension have inappropriately low and 20% have inappropriately high plasma renin activity. Blood pressure of patients with high-renin hypertension responds well to drugs that interfere with the system, supporting a role for excess renin and angiotensin in this population. 

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