HEPARIN INHIBITS MESENTERIC VASCULAR HYPERTROPHY IN ANGIOTENSIN II-INFUSION HYPERTENSION IN RATS

Objective: Chronic infusion with angiotensin II increases blood pressu re and activates growth mechanisms to produce hypertrophy of the heart and vessels. In order to better understand mechanisms of angiotensin II induced vascular hypertrophy, this study aimed to determine whether heparin, a potent inhibitor of smooth muscle proliferation mechanisms , was able to inhibit vascular hypertrophy. Methods: Angiotensin II (1 00, 200 or 300 ng/min/kg s.c,) or a saline vehicle control were infuse d into rats for 14 days. A separate group of animals were co-infused w ith heparin (0.3 mg/h/kg i.v.) and angiotensin II (200 ng/min/kg s.c.) to test whether hypertension or hypertrophy were antagonized. Blood p ressure was measured by tail cuff method and vessel media cross sectio nal area was measured by morphometry in aorta and mesenteric arteries. Results: Blood pressure elevation and cardiovascular hypertrophy prod uced by angiotensin II were strongly dose-dependent. Hypertrophy respo nses at 14 days of treatment also appeared to be influenced partly by local factors as medial cross sectional area was increased more in mes enteric arteries than in thoracic aorta, and left ventricle weight was least affected. Heparin treatment did not influence the increase of b lood pressure in angiotensin II infused animals, but the mesenteric va scular hypertrophy response due to angiotensin II was inhibited by app roximately 50%. Inhibition of a modest cardiac hypertrophy and aortic medial hypertrophy did not reach significance. Conclusions: Angiotensi n II infusion produced vascular medial hypertrophy and increased blood pressure, however the inhibitory effect of heparin on hypertrophy in mesenteric arteries was not mediated through angiotensin II induced va soconstriction or blood pressure elevation. These data suggest that he parin interferes directly with the hypertrophy mechanism in mesenteric arteries, and that heparin-sensitive growth mechanisms are important in mediating angiotensin induced mesenteric vascular hypertrophy. (C) 1998 Elsevier Science B.V.