Affecting the Renin-Angiotensin System

ACE inhibitors are now considered one of the mainstays of treatment in congestive heart failure. These drugs are the first agents shown to prolong the life span of people with this disease 60 that is, digitalis, diuretics, and other drugs commonly used to treat heart failure may all produce symptomatic improvements, but the use of ACE inhibitors alone or in combination with these drugs actually results in decreased mortality.32,60 

The use of ACE inhibitors in treating heart failure has therefore increased dramatically over the last several years.53 There is evidence that these drugs should be used even more extensively and in higher doses, especially in the early stages of this disease.32,48 By reducing the detrimental effects of angiotensin II on the vascular system, early use of ACE inhibitors may prevent or delay the progression of this disease (see the next section, Effects and Mechanism of Action of ACE Inhibitors ). 

Angiotensin II also promotes abnormal growth and remodeling of the heart, and this substance is thought to be responsible for many of the pathologi- 

Finally, ACE inhibitors exert some of their beneficial effects by increasing bradykinin levels in the bloodstream.17,70 Bradykinin is a vasodilator, and increased levels of this compound decrease cardiac workload in people with heart failure. Normally, ACE is responsible for the enzymatic destruction of bradykinin in the bloodstream. ACE inhibitors reduce the breakdown of bradykinin, thereby prolonging the vasodilating effects of this substance.17,70 

ACE inhibitors reduce the detrimental effects of excess angiotensin II and aldosterone, and prolong the beneficial effects of bradykinin. These effects work in combination to sustain cardiovascular health in people with heart failure. 

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Q9 All of the following drugs affect the renin—angiotensin system... 

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

Hypertensive patients with normal or high renin levels can benefit from treatment with agents which affect the renin-angiotensin system. 

Introduction - The search for new antihypertensives and for a better understanding of existing ones remains quite intense with emphasis this past year on 3-blockers (see Chapter 9) and on agents that affect the renin-angiotensin system. Diuretics were reviewed last year and are not included in this chapter. Structures of drugs mentioned in this review are shown or may be found in recent volumes of Annual Reports in Medicinal Chemistry. 

In view of his cardiovascular status and proteinuria, WD should be on anti-ACE therapy of some kind. If he is unable to tolerate an ACE inhibitor, an alternative might be to try an ARB. This has the advantage of blocking the renin-angiotensin system, thereby achieving the required therapeutic effect, but since ACE itself is not affected, the patient should not develop a cough. 

In the initiation phase of acute renal failure, mitochondrial oxygen uptake is affected by ischemia. The resulting vasoconstriction in the kidney activates the renin-angiotensin system. The intracellular calcium level in the mitochondria increases. The administration of a calcium transport blocker such as Verapamil can reverse or prevent renal vasoconstriction and also restore the mitochondrial oxygen uptake and thus prevent cell necrosis and the development of the maintenance phase of acute renal failure. 

Marked decreases in blood pressure may affect renal function, and in addition, the renin-angiotensin system plays an important role in the maintenance of the glomerular filtration rate when renal artery pressure is... 

Lead exposure affects BP through the renin—angiotensin system as studied in male adult rats (Boscolo and Carmignani, 1988 Rodriguez-Iturbe et al., 2005). Rodriguez-lmrbe et al. noted that the effects of Pb on the... 

Nephrotoxins that cause tubular necrosis may indirectly induce vasoconstriction and reduce renal blood flow. These changes may occur because alteted delivery of solutes to the distal nephron affects the action of prostaglandins and the renin-angiotensin system. 

The renin-angiotensin system is not affected by clwiges that occur in CFR during acute renal failure. 

Ovarian hormones influence fluid intake by interaction with the brain renin-angiotensin system and it has been shown that gonadal steroids affect brain fluid-electrolyte balance by interactions with vasopressin. Both hyperos-molarity and increased intracranial pressure stimulate vasopressin release and intraperitoneal administration of vasopressin antagonists decrease brain volume. 

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