Clinical Applications of Angiotensin-Converting Enzyme Inhibitors

737

ANDROLOGY

DISEASES OF BLOOD VESSELS, HYPERTENSION AND RENOV ASCULAR SURGERY

Cal'diovascula:r Effects of Pu.trescine in. Dogs Afte:r Systemic, Intra-Arterial Vertebral and Intraventricular Injection F. ROSSI,

G. NISTICO, G. DEMARCO, L. BERRINO, C. G. BILE AND E. MARMO, Institute of Pharmacology and Toxicology, University of Naples, Naples, and Institute of Pharmacology, University of Catanzaro, Catanzaro, Italy

Clinical Applications of Angiotensin-Converting Enzyme Inhibitors

R. K. FERGUSON, P. H. VLASSES AND H. H. ROTMENSCH, Division of Clinical Pharmacology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania Amer. J. Med., 77: 690-698 (Oct.) 1984 To date, the clinical applications of angiotensin-converting enzyme inhibitors have been in the treatment of refractory hypertension and congestive heart failure. These substances were developed to inhibit selectively the conversion of angiotensin I to angiotensin II in plasma and tissues, and to diminish the contribution of the renin-angiotensin-aldosterone system to blood pressure and volume maintenance. The introduction of captopril in 1981 proceeded directly from the isolation and effect of the parenteral enzyme inhibitor teprotide, a snake venom extract. The newer inhibitors, such as enalapril maleate and MK-521, do not contain a sulfhydryl group in the structure, which may produce fewer side effects. This evaluation shows that angiotensin-converting enzyme inhibitors are useful in the treatment of most forms of hypertension and congestive heart failure refractory to digitalis and diuretics. They also are useful in scleroderma renal crisis, renovascular hypertension and coarctation of the aorta that activates the renin-angiotensin-aldosterone system. There also is evidence that these substances may be useful in idiopathic edema and Bartter's syndrome, in which abnormalities of the renin-angiotensin-aldosterone system may have a role. There seems to be little value in primary pulmonary hypertension and acute renal failure. Further evaluation of the importance of these angiotensin-converting enzyme inhibitors may be improved by the use of the newer nonsulfhydryl agents. F. T. A. 104 references Inhibition of Angiotensin-Convel'ting Enzyme by Dipeptide Analogs MACERATA, W. ROGERS, J. BARTON, J. A. KHANDW ALA, Research and Development Division of Revlon Health Care Group, Tuckahoe, New York

A. SCHWAB,

R.

SKILES AND

Res. Comm. Chem. Path. Pharm., 45: 339-345 (Sept.) 1984 Several inhibitors of the angiotensin-converting enzyme have been shown to be effective as antihypertensive agents. Therefore, information about the specificity of the angiotensin-converting enzyme toward substrates and inhibitors can be useful in the design of more potent angiotensin-converting enzyme inhibitors and hopefully more potent antihypertensive agents. The angiotensin-converting enzyme is highly specific with respect to the amide terminal and carboxyl terminal amino acid residue of the dipeptide. Some dipeptide analogues that contain an acyclic tertiary amide group and p-tolyl or norbornyl substitute on the amide nitrogen atom are effective angiotensinconverting enzyme inhibitors. N. V. R. 2 figures, 1 table, 7 references

MATERA,

Res. Comm. Chem. Path. Pharm., 46: 43-52 (Oct.) 1984 Putrescine is an aliphatic amine largely distributed in living organisms and suggested to have a role as a transmitter or modulator in the central nervous system. In anesthetized dogs higher doses of putrescine than other transmitters were required to produce cardiovascular effects. Injection of putrescine into the third cerebral ventricle and the vertebral artery produced a dose-dependent hypotensive response, which was accompanied by tachycardia when given intravenously and bradycardia after intraventricular infusion or injection in the vertebral artery. This finding presumably was owing to an increase in parasympathetic output. The hypotensive response after intravenous injection appeared to be due to histamine release, and tachycardia appeared to be due to the release of histamine and a reflex stimulation of the carotid-sinus baroreceptors. W. J.C. 7 tables, 13 references

PREOPERATIVE AND POSTOPERATIVE THERAPY N aftidroforyl and the Nitrogen, Carbohydrate and Lipid Responses to Moderate Surgery

J.

H. T. KHAWAJA, P. C. WEAVER, s. T. H. A. LEE, Department of Renal and Metabolic Medicine, University of Southhampton and Department of Surgery, St. Mary's Hospital, Portsmouth, England M. JACKSON, TALBOT AND

Brit. Med. J., 289: 581-586 (Sept. 8) 1984

It has been reported previously that naftidrofuryl prevented the nitrogen loss associated with an operation. In this study 45 patients undergoing an elective intra-abdominal operation were given either a placebo or 200 mg. naftidrofuryl twice daily, beginning with the induction of anesthesia or on the morning after the operation. No difference in urinary nitrogen excretion between the controls and patients given the drug was found. The lactate-to-pyruvate ratio was significantly lower in the treated group. No other differences were noted. The authors made no comment on the nature or mode of action of this type of drug. J. A. A. 3 tables, 15 references

ANDROLOGY Gynecomastia in a Hospitalized Male Population C. B. NIEWOEHNER AND F, Q. NUTTALL, Endocrine-Metabolic Section, Veterans Administration Medical Center and Department of Medicine, The University of Minnesota, Minneapolis, Minnesota

Amer. J. Med., 77: 633-638 (Oct.) 1984