When Is It Useful to Inhibit the Renin-Angiotensin System for Treating Hypertension?

Summary: The acute, 60 min blood pressure and plasma renin responses to an oral test dose of captopril given to a quietly seated patient can be used to gain information quickly on renin dependency or lack of it in a hypertensive situation. This information is verified by a baseline renin sodium profile text. These two diagnostic steps define either renin dependency or a sodium-volume mechanism involved in the vasoconstrictor. At the same time they also enable the complete diagnosis or exclusion of curable renovascular disease. For long-term therapy, pharmacologic inhibition of the renin-angiotensin system can be accomplished by or using converting enzyme inhibitors to block angiotensin II formation or beta receptor blocking drugs to block renin secretion and by combining the two. Inhibition of the renin-angiotensin system is the logical first step in antihypertensive drug therapy, both for acute hypertensive emergencies or chronic therapy, whenever the hypertension is largely or significantly renin dependent, i.e., in the high and normal renin forms of hypertension. This includes up to 70% of patients with essential hypertension. If converting enzyme inhibition or beta blockade is only partially effective, the two can be combined to achieve more complete blockade. A more popular alternative to this has been the addition of a diuretic as the second drug. However, this introduces well-known problems of diuretic therapy including dehydration, which eliminates the conceptual advantage of pure blockade of renin-mediated vasoconstriction, i.e., reducing pressure without reducing tissue flow. Renin system inhibition in addition to this primary role in diagnosis and treatment of hypertension has a rational secondary role in therapy, i.e., dealing specifically with poor responses to other types of antihypertensive agents. Thus, the marked reactive hyperreninemia induced by diuretics or the nonspecific vasodilators is the basis for their lack of effectiveness. This compensation is removed by adding antirenin system therapy. These primary and secondary indications for antirenin system therapy are equally applicable in congestive heart failure with or without hypertension, where the operant renin profile similarly reveals renin dependency, or its absence, thereby allowing the physician to choose either antirenin therapy to block renin-mediated vasoconstriction or to use alternative therapy in low renin patients directed primarily against the sodium-volume mediated form of vasoconstriction, viz., diuretics or calcium channel blocking drugs.