saralasin and Hyperplasia

Increasing evidence points toward local production of renin and angiotensinogen in the artery wall. Because angiotensin converting enzyme (ACE) inhibitors have been shown to block intimal hyperplasia after arterial injury in the rat, it has been suggested that angiotensin II is an important mediator of the proliferative response to vascular injury. To prove that previous observations with use of ACE inhibitors are a result of effects on local angiotensin levels versus nonspecific drug effects, we tested the ability of an unrelated drug, the angiotensin II receptor antagonist saralasin, to similarly block intimal hyperplasia after aortic injury in the rat. Balloon catheter aortic denudation was performed in 28 rats pharmacologically treated for 14 days after surgery and split into four groups: group 1, saralasin 360 micrograms/kg/hr intravenously; group two, normal saline 0.5 mm3/hr intravenously; group 3, captopril 100 mg/kg/day orally; and group 4, heparin 50 U/kg/hr intravenously. Animals were killed and aortas were perfusion fixed at physiologic pressure 14 days after denudation. Cross-sectional intima-to-media ratios were calculated by computerized planimetry. Compared with saline controls, saralasin inhibited intimal hyperplasia 45% (p less than 0.001), captopril 59% (p less than 0.001), and heparin 68% (p less than 0.001). A reduction in total intimal area was also evident in animals treated with saralasin (p less than 0.01). Blood pressure in the group treated with captopril decreased from 107.4 +/- 3.9 to 96.3 +/- 4.3 mm Hg (p less than 0.01) after 6 days, whereas saralasin and heparin had no effect on blood pressure. Weight gain during the study was reduced in groups treated with captopril and heparin but not in the group treated with saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Animals; Aorta; Hyperplasia; Male; Muscle, Smooth, Vascular; Rats; Rats, Inbred Strains; Saralasin

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aldosterone; Desoxycorticosterone; Female; Fludrocortisone; Humans; Hyperaldosteronism; Hyperplasia; Male; Middle Aged; Posture; Potassium; Saralasin; Sodium; Sodium Chloride

Arteriography in two patients with renovascular hypertension suggested fibromuscular hyperplasia, mainly affecting the right renal artery. When saralasin was infused intravenously there was no fall in blood-pressure in either patient. However, both had a raised renal-vein plasma-renin activity on the affected side, relative to the unaffected kidney. Auto-transplantation resulted in a sustained reduction in arterial pressure in both patients. A negative saralasin test should not necessarily exclude further investigation of young patients with severe hypertension.

Topics: Adult; Angiography; Angiotensin II; Blood Pressure; Blood Pressure Determination; Evaluation Studies as Topic; Female; Humans; Hyperplasia; Hypertension, Renal; Kidney; Kidney Transplantation; Male; Prognosis; Renal Artery; Renal Veins; Renin; Saralasin; Transplantation, Autologous

Topics: Angiotensin II; Blood Pressure; Humans; Hyperplasia; Hypertension, Renal; Kidney; Kidney Diseases; Regional Blood Flow; Renal Artery Obstruction; Renal Veins; Renin; Saralasin

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Gland Diseases; Adrenocorticotropic Hormone; Cushing Syndrome; Female; Humans; Hydrocortisone; Hyperaldosteronism; Hyperplasia; Hypertension; Hypokalemia; Hypothalamo-Hypophyseal System; Methods; Middle Aged; Saralasin