The receptors and role of angiotensin II in knee joint blood flow regulation and role of nitric oxide in modulation of their function.
OBJECTIVE
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 (AT(1)) receptor antagonist losartan did not change the basal JVR but completely blocked the effect of angII on JVR. N(omega)-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 AT(1) subtype 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 AT(1) receptor-mediated vasoconstriction of joint blood vessels.
Najafipour
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Department of Physiology and Cardiovascular Research Center, Kerman University of Medical Sciences, Kerman, Iran. najafipourh@kmu.ac.ir
Ketabchi
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F
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D007719:Knee Joint / Q000098:blood supply*; D019808:Losartan / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D009569:Nitric Oxide; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester