Abstract
Objectives:Angiotensin-converting enzyme (ACE) upregulation in the stroma cells of arthritis rheumatoid joints may produce a higher tissue concentration of angiotensin II (angII), which is a vasoconstrictor and mitogen factor that causes local hypoxia and synovial proliferation. No study in the literature has examined the role of angII in joint blood flow (JBF) regulation and the potential effect of ACE inhibitors on JBF. Methods:The study was performed on 20 Dutch white rabbits to examine the JBF response to angII, angII receptor subtypes, and the role of nitric oxide (NO) in angII effects in knee joint blood vessels. Drugs were administered locally through retrograde saphenous artery cannulation. Joint vascular resistance (JVR) was calculated by dividing the arterial blood pressure by the JBF. Results:AngII increased JVR dose dependently. The angII type 1 (AT1) receptor antagonist losartan did not change the basal JVR but completely blocked the effect of angII on JVR. Nω-nitro-L-arginin methyl ester (L-NAME) increased JVR by a mean (±SEM) of 25.8 ± 8.7% (p< 0.05) but did not affect the joint vessel response to angII and losartan. Conclusions:AngII receptors are from the AT1subtype in normal joint blood vessels, but angII plays no significant role in JBF regulation. The basal release of NO plays a role in resting JBF regulation, but NO does not affect the AT1receptor-mediated vasoconstriction of joint blood vessels. Microcirculation(2003) 10,383–390. doi:10.1038/sj.mn.7800205