The Renin-Angiotensin System

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... 

Bader M, Paul M, Fernandesz-Alfonso M et al (1994) Molecular biology and biochemistry of the renin-angiotensin system, Chap. 11. In Swales ID (ed) Textbook of hypertension. Blackwell Scientific Publications, Oxford, London, Edinburgh, pp 214-232... 

Hermann K, Ring J The renin-angiotensin system in patients with repeated anaphylactic reactions during Hymenoptera venom hyposensitization and sting challenge. Int Arch Allergy Immunol 1997 11 251-256. 

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

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, Shulak JM, et al. 1982b. Lead, hypertension, and the renin-angiotensin system in rats. J Clin Med 99 354-362. 

Beige J, Zilch O, Hohenbleicher H, Ringel J, Kunz R, Distler A, Sharma AM. Genetic variants of the renin-angiotensin system and ambulatory blood pressure in essential hypertension. J Hypertens 1997 15 503-508. 

Van Ampting JMA, Hijmering ML, Beutler JJ, van Etten RE, Koomans HA, Rabelink TJ, Stroes ESG. Vascular effects of ACE inhibition independent of the renin-angiotensin system in hypertensive renovascular disease. Hypertension 2001 37 40-45. 

Regardless of the etiology, fall in blood pressure (BP) is compensated by an increase in sympathetic outflow, activation of the renin-angiotensin system, and other humoral factors that stimulate peripheral vasoconstriction. Compensatory vasoconstriction redistributes blood away from the skin, skeletal muscles, kidneys, and GI tract toward vital organs (e.g., heart, brain) in an attempt to maintain oxygenation, nutrition, and organ function. 

The development of ascites is related to systemic arterial vasodilation that leads to the activation of the baroreceptors in the kidney and an activation of the renin-angiotensin system, with sodium and water retention and vasoconstrictor production. 

Kurz, S., Hink, U., Nickenig, G., Borthayre, A. B., Harrison, D. G., Munzel, T., Evidence for a causal role for the renin-angiotensin system in nitrate tolerance. Circulation 99 (1999), p. 3181-3187... 

The activity of the renin-angiotensin system is reduced with age (Muhlberg and Platt 1999). The ability of the kidney to concentrate urine maximally after water deprivation decreases with age, as does the ability to excrete a water and salt load, particularly during the night. Nocturnal polyuria is common in the elderly (Lubran 1995). Diuretics are commonly used in the elderly. There is an increased risk for hypokalemia and hyponatremia from diuretics in the elderly (Passare et al. 2004). Electrolyte disturbances may also be caused by several types of drugs in the elderly and it is important to monitor serum electrolyte levels in the elderly. Treatment with... 

The interest in these peptides and others whose mechanisms of action are not yet so clearly defined is evident from the many recent publications. Since the peptides are not orally active, their role in the treatment of hypertension is uncertain at this point. Their value as diagnostic tools has been established. For example, the use of saralasin in the recognition of angiotensinogenic hypertension in man has been demonstrated (103). Perhaps of greater value will be the role of these compounds and peptides still to come in defining the importance of the renin-angiotensin system in the etiology of hypertension and the control of blood pressure. 

Factors which have been considered responsible for this hemodynamic alteration are heredity, salt and water, the adrenergic nervous system and the renin-angiotensin system. 

In addition, there is now good evidence indicating that methyldopa effectively suppresses the release of renin by the kidney(23,24). This effect may contribute to the antihypertensive efficacy of the drug in some hypertensive states in which the renin-angiotensin system plays a pathophysiologic role. Thus, it may be concluded that a) methyldopa lowers the blood pressure... 

Structure and physiology of the kidney glomerular filtration tubular activity selective reabsorption and secretion, often using specific carrier mechanisms carbonic anhydrase and acid-base balance. The kidney also produces, and is sensitive to, hormones actions of the hormones ADH, aldosterone and PTH the kidney as a secretory organ erythropoietin, the renin-angiotensin system vitamin D3. 

E. H. Ulm, W. J. Greenlee, Inhibitors of the Renin-Angiotensin System Enzymes , in Design of Enzyme Inhibitors as Drugs , Eds. M. Sandler, H. J. Smith, Oxford University Press, Oxford, 1989, p. 146- 177. 

Among antihypertensives, those targeting the renin-angiotensin system are among the best studied. The renin-angiotensin system consists of a two-enzyme cascade that is involved in the regulation of blood pressure and electrolyte homeostasis. 

Wang, J. G., and Staessen, J. A. (2000) Genetic polymorphisms in the renin-angiotensin system relevance for susceptibility to cardiovascular disease. Eur. J. Pharmacol. 410, 289-302. 

Andrikopoulos, G.K., Richter, D.J., Needham, E.W., et al., GEMIG study investigators. (2004) The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction. Eur. J. Cardiovasc. Prev. Rehabil. 11, 477-483. 

Nishikino, M., Matsunaga, T., Yasuda, K., et al. (2006) Genetic variation in the renin-angiotensin system and autonomic nervous system function in young healthy lapanese subjects. J. Clin. Endocrinol. Metab. 91, 4676 681. 

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