THE EFFECTS OF PERFUSION RATE AND N-G-NITRO-L-ARGININE METHYL-ESTER ON CIRAZOLINE-INDUCED AND KCL-INDUCED RESPONSES IN THE PERFUSED MESENTERIC ARTERIAL BED OF RATS
Aso. Adeagbo et al., THE EFFECTS OF PERFUSION RATE AND N-G-NITRO-L-ARGININE METHYL-ESTER ON CIRAZOLINE-INDUCED AND KCL-INDUCED RESPONSES IN THE PERFUSED MESENTERIC ARTERIAL BED OF RATS, British Journal of Pharmacology, 111(1), 1994, pp. 13-20
1 The purpose of this study was to characterize the effects of NG-nitr
o-L-arginine methyl ester (L-NAME) on the perfusion rate/pressure rela
tions, and on the presser responses induced to cirazoline and KCI in i
solated, perfused mesenteric arterial beds from normotensive and spont
aneously hypertensive rats. 2 The basal perfusion pressure of arterial
beds perfused with either physiological salt solution (PSS) or PSS co
ntaining 1% polyvinylpyrrolidone increased as the perfusion rate incre
ased. L-NAME, in concentrations up to 100 mu M, failed to alter the ba
sal pressure regardless of the perfusion rate and viscosity; however,
at 5 mu M, it potentiated cirazoline-induced vasoconstriction at each
of the perfusion rates. 3 L-NAME but not D-NAME caused a leftward shif
t of cirazoline concentration-response curves with a marked increase i
n the maximal response. The potentiating action of L-NAME was abolishe
d in arterial beds perfused with a Ca2+-free physiological salt soluti
on and also in beds denuded of endothelium by an infusion of distilled
water for 5 min. 4 In endothelium-intact and -denuded preparations, L
-NAME potentiated KCI presser responses; the endothelium-independent p
otentiation of KCl presser activity was stereospecific, time-independe
nt and was not prevented by the presence of dexamethasone (0.5 mu M) i
n the perfusion medium. However, L-NAME failed to potentiate vasoconst
riction obtained to KCI in arterial beds denervated by cold storage (4
-5 degrees C) for 2 days. 5 The absence of K+ in the perfusate did not
inhibit the ability of L-NAME to potentiate alpha-adrenoceptor-mediat
ed presser responses, and nor did L-NAME inhibit KCl-induced vasodilat
ation in preconstricted arteries. It was thus concluded that L-NAME do
es not affect Na+/K+-ATPase activity. 6 No differences in the potentia
ting ability of L-NAME on either cirazoline- or KCl-mediated presser r
esponses were apparent between normotensive Sprague Dawley (SD), Wista
r Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 7 Our data th
us provide evidence that: the presence of a vasoconstrictor is require
d for basal nitric oxide (NO) release in the mesenteric arterial bed f
rom either normotensive or spontaneously hypertensive rats; L-NAME cau
ses potentiation of cirazoline- and KCl-induced vasoconstriction respe
ctively by inhibiting endothelial and neuronal NO synthase(s). Further
more, our data indicate that NO synthase activity is not impaired in t
he mesenteric arterial bed of spontaneously hypertensive rats.