J. Gillongo et al., STUDY OF IN-VIVO AND IN-VITRO RESTING VASODILATOR NITRIC-OXIDE TONE IN NORMOTENSIVE AND GENETICALLY HYPERTENSIVE RATS, European journal of pharmacology, 310(2-3), 1996, pp. 175-183
The effects of N-G-nitro-L-arginine (L-NNA) on mean arterial pressure
and the effects of both L-NNA and methylene blue on isolated aorta ton
e, were studied in order to elucidate potential alterations in vasodil
ator resting nitric oxide (NO) tone in genetic hypertension. L-NNA pro
duced a significantly greater increase of mean arterial pressure in sp
ontaneously hypertensive rats (SHR) than in Wistar Kyoto (WKY) rats; i
n both cases, L-arginine completely inhibited the L-NNA hypertensive e
ffect. Neither ganglion blockade with hexamethonium nor cyclooxygenase
inhibition with indomethacin significantly modified the effect of L-N
NA in both rat strains. In intact aorta rings, after submaximally cont
raction with KCl (25 mM), both L-NNA and methylene blue induced strong
dose-dependent contractions. The maximum contractions were, however,
significantly greater in WKY rats than in SHR. The mechanical eliminat
ion of endothelium markedly inhibited both L-NNA and methylene blue ma
ximum contractions. In intact rings, L-arginine completely inhibited t
he L-NNA effects in both rat strains; in rubbed rings, the L-arginine
inhibitory effects were strong in WKY rats but not important and errat
ic in SHR. L-Arginine had no effect on the contractions induced only b
y KCl in any of the preparations. In WKY rat-rubbed rings, sodium nitr
oprusside was significantly more effective in relaxing the contraction
s in response to 25 mM KC1 than the contractions in response to methyl
ene blue. These results indicate that contractions induced by L-NNA an
d methylene blue in isolated aorta are principally due to the inhibiti
on of an important endothelial resting vasodilator NO tone. They also
show that hypertension reduces the resting vasodilator NO tone in isol
ated rat aorta, in spite of enhancing the total vasodilator NO tone in
anaesthetized rat.