Cardiovascular hypertrophy in one-kidney, one-clip renal hypertension is resistant to heparin.
OBJECTIVE
Heparin inhibits vascular hypertrophy in angiotensin-induced hypertension, in addition to its well-known role in inhibiting injury-induced vascular smooth muscle proliferation. We tested whether hypertension and vascular hypertrophy could be reduced by heparin independently from the renin-angiotensin system.


METHODS
Rats were made hypertensive with a one-kidney, one-clip (1K1C) procedure and received heparin from osmotic minipumps (0.3 mg/h per kg i.v.) or saline vehicle for 2 weeks. Blood pressure was measured by the tail-cuff method and vessel cross-sectional area was measured by morphometry in the aorta and mesenteric arteries. Proliferation was assessed with bromodeoxyuridine labelling.


RESULTS
Blood pressure elevation and cardiovascular hypertrophy were evident in 1K1C rats. The media of mesenteric arteries was increased by 25%, and the media : lumen ratio by 35%, in hypertensive rats. DNA synthesis by smooth muscle cells in the mesenteric arteries was increased sevenfold in renal hypertension. Heparin treatment did not influence either the increase in blood pressure, the cardiovascular hypertrophy response or hypertension-mediated proliferation of arterial smooth muscle cells.


CONCLUSIONS
These data suggest that the vascular hypertrophy mechanisms operating in 1K1C renal hypertension are not inhibited by heparin and thus are different from those in angiotensin-mediated hypertension. Identifying such mechanisms in the future will be important for devising appropriate intervention strategies in angiotensin-independent forms of vascular hypertrophy.
Dilley
Rodney J
RJ
Morphology Laboratory, Baker Heart Research Institute, Prahran, Australia. rod.dilley@baker.edu.au
Rizkalla
Bishoy
B
Bertram
John F
JF
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D006493:Heparin / Q000627:therapeutic use*; D006977:Hypertension, Renal / Q000378:metabolism*; D006984:Hypertrophy; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors
D000804:Angiotensin II; D006493:Heparin; D004247:DNA