Peptides are used by most tissues for cell-to-cell communication. As noted , they play important roles as transmitters in the autonomic and central nervous systems. Several peptides exert important direct effects on vascular and other smooth muscles. These peptides include vasoconstrictors (angiotensin II, vasopressin,endothelins, neuropeptide Y, and urotensin) and vasodilators(bradykinin and related kinins, natriuretic peptides, vasoactiveintestinal peptide, substance P, neurotensin, calcitonin gene-related peptide, and adrenomedullin).
During a routine check, a 45-year-old man was found to have high blood pressure (165/100 mm Hg). Blood pressure remained high on two follow-up visits. His physician initially prescribed hydrochlorothiazide, a diuretic commonly used to treat hypertension. Although his blood pressure was reduced by hydrochlorothiazide, it remained at a hypertensive level (145/95 mm Hg), and he was referred to the university hypertension clinic. Your evaluation reveals that the patient has elevated plasma renin activity and aldosterone concen-tration. Hydrochlorothiazide is therefore replaced with enalapril, an angiotensin-converting enzyme inhibitor. Enalapril lowers the blood pressure to almost normotensive levels. However, after several weeks on the new drug, the patient returns complaining of a persistent cough. In addition, some signs of angioedema are detected. How does enalapril lower blood pressure? Why does it occasionally cause cough-ing and angioedema? What other drugs could be used to inhibit renin secretion or suppress the renin-angiotensin system, and decrease blood pressure, without the adverse effects of enalapril
CASE STUDY ANSWER
Enalapril lowers blood pressure by blocking the conversion of angiotensin I to angiotensin II (ANG II). Since converting enzyme also inactivates bradykinin, enalapril increases bra-dykinin levels, and this is responsible for adverse side effects such as cough and angioedema. This problem could be avoided by using a renin inhibitor, eg, aliskiren, or an ANG II receptor antagonist, eg, losartan, instead of an ACE inhibitor, to block the renin-angiotensin system.