Renin-angiotensin system effects

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). 

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. 

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... 

Matsui T, Hayashi A, Tamaya K, Matsumoto K, Kawasaki T, Murakami K, Kimoto K. (2003) Depressor effect induced by dipeptide, Val-Tyr, in hypertensive transgenic mice is due, in part, to the suppression of human circnlating renin-angiotensin system. Clin Exp Pharmacol Physiol 30 262-265. 

The naturally occurring mineralocorticosteroid is aldosterone. Its release is not ACTH dependent but is stimulated under control of the renin-angiotensin system. Aldosteron is not in clinical use because of its short halflife (20 min). Fludrocortisone is a synthetic analogue with considerably more potent mineralocorticoid than glucocorticoid activity. It is used as substitution therapy in adrenocorticoid insufficiency and in low-renin hypoaldosteronism. It is well absorbed orally and its effects last 1-2 days. 

Inhibition of the renin-angiotensin system with ACE inhibitors or ARBs may be incomplete because the drugs disrupt the negative feedback action of Ang II on renin secretion and thereby increase plasma renin activity. Other antihypertensive drugs, notably hydrochlorothiazide and other diuretics, also increase plasma renin activity. Aliskiren not only decreases baseline plasma renin activity in hypertensive subjects but also eliminates the rise produced by ACE inhibitors, ARBs, and diuretics and thereby results in a greater antihypertensive effect (Figure... 

Taken together these investigations point to a possible influence of the renin-angiotensin system on cardiac cellular coupling. According to De Mello [1992, 1994] it can be argued that at least in parts the positive effects of... 

De Mello WC The role of the renin angiotensin system in the control of cell communication in the heart Effects of enalapril and angiotensin II. J Cardiovasc Pharmacol 1992 20 643-651. 

Particularly when androgens/anabolics are misused to promote extreme muscular development, there is a risk of cardiomegaly and ultimate cardiac failure. Androgen-induced hypertension may be due to a hypertensive shift in the pressure-natriuresis relation, either by an increase in proximal tubular reabsorption or by activation of the renin-angiotensin system (27). This effect is not related to higher doses or longer treatment and can develop after a few months but can also be delayed for many years. 

Morelli A, Tritapepe L, Rocco M, Conti G, Orecchioni A, De Gaetano A, Picchini U, Pelaia P, Reale C, Pietropaoli P. Terlipressin versus norepinephrine to counteract anesthesia-induced hypotension in patients treated with renin-angiotensin system inhibitors effects on systemic and regional hemodynamics. Anesthesiology 2005 102 12-19. 

Fluid depletion may also be a serious problem during diuretic therapy. A decrease in blood volume may cause a reflex increase in cardiac output and peripheral vascular resistance because of activation of the baroreflex (see Chapter 18). This occurrence may produce an excessive demand on the myocardium, especially in patients with cardiac disease. Decreased blood volume may also activate the renin-angiotensin system, thereby causing further peripheral vasoconstriction and increased cardiac workload. Again, the effects of fluid depletion may be especially serious in patients with certain types of heart failure. 

Adverse Side Effects of Drugs Affecting the Renin-Angiotensin System... 

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