1. Role of protein kinase C in electrical-stimulation-induced neuronal nitric oxide release in mesenteric arteries from hypertensive rats
J Marín, M Ferrer, G Balfagón Clin Sci (Lond). 2000 Oct;99(4):277-83.
This study examines the influence of hypertension on neuronal nitric oxide (NO) release and its modulation by protein kinase C (PKC). For this purpose, mesenteric segments without endothelium were obtained from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), and neurogenic NO release induced by electrical field stimulation (EFS) was examined in these segments. EFS induced frequency-dependent contractions. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the sensorial neurotoxin capsaicin increased EFS-induced contractions in SHR segments, but did not affect these contractions in segments from WKY rats. In segments from SHRs, the increase in EFS-induced response by capsaicin was further increased by the combination of capsaicin and L-NAME. EFS-induced contractions in SHR arteries were unaltered by the protein synthesis inhibitor cycloheximide or by 2-amine-5,6-dihydro-6-methyl-4H-1,3-tiazine (AMT), an inhibitor of inducible NO synthase, and increased by the guanylate cyclase inhibitor Methylene Blue. In these arteries, capsaicin plus the PKC inhibitor calphostin C increased the contractions elicited by EFS; the addition of L-NAME did not affect this increase. Phorbol 12,13-dibutyrate (PDBu) did not modify the response to EFS in these arteries pretreated with capsaicin, although a combination of PDBu and L-NAME was effective. These results indicate that, in mesenteric arteries, EFS induces the release of NO from perivascular nitrergic nerves and of neuropeptides from sensory nerves, but only in hypertensive rats. The NO released is synthesized by constitutive neuronal NO synthase in a manner that is positively modulated by PKC, an enzyme that seems to be activated in hypertension.
2. Endogenous prostacyclin increases neuronal nitric oxide release in mesenteric artery from spontaneously hypertensive rats
Mercedes Ferrer, Mercedes Salaices, Gloria Balfagón Eur J Pharmacol. 2004 Dec 15;506(2):151-6. doi: 10.1016/j.ejphar.2004.11.001.
The aim of this study was to analyse the possible influence of endogenous prostacyclin on neuronal nitric oxide (NO) release induced by electrical field stimulation in mesenteric arteries from spontaneously hypertensive rats (SHR). Preincubation with the prostacyclin synthesis inhibitor tranylcypromine decreased NO release induced by electrical field stimulation, which was reversed by exogenous prostacyclin. Preincubation with tranylcypromine increased basal and electrical field stimulation-induced [3H]noradrenaline release. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl esther (L-NAME) increased the vasoconstrictor response induced by electrical field stimulation. In the presence of tranylcypromine, L-NAME did not modify the vasoconstrictor response induced by electrical field stimulation. In the presence of tranylcypromine and prostacyclin, LNAME increased the vasoconstrictor response to electrical field stimulation. These results indicate that endogenous prostacyclin positively modulates the neuronal NO release induced by electrical field stimulation and that this neuronal NO participates in the regulation of the vasomotor response.
3. Aging increases neuronal nitric oxide release and superoxide anion generation in mesenteric arteries from spontaneously hypertensive rats
Mercedes Ferrer, Margarita Sánchez, Nuria Minoves, Mercedes Salaices, Gloria Balfagón J Vasc Res. 2003 Nov-Dec;40(6):509-19. doi: 10.1159/000075183. Epub 2003 Nov 27.
We hypothesized that neuronal NO release as well as its bioavailability and vasomotor response could be affected when aging and hypertension are present simultaneously. The neuronal nitric oxide (NO) release, its metabolism and vasomotor response induced by electrical field stimulation was analyzed in isolated segments of endothelium-denuded mesenteric arteries from young and old spontaneously hypertensive rats (SHR). The nitric oxide synthase (NOS) inhibitor N(G)-nitro-arginine-methyl ester (L-NAME) and NOS inhibitor 7-nitroindazole both strengthened electrical field stimulation-elicited contractions more in arteries from young than aged SHR rats. Superoxide dismutase (SOD) potentiated the L-NAME effect in segments from old rats, whereas catalase decreased the contractions induced by electrical field stimulation and noradrenaline but did not modify the L-NAME effect. In noradrenaline-precontracted segments, sodium nitroprusside induced a similar relaxation in arteries from both experimental groups. This relaxation was increased by SOD in old SHR. 8Br cGMP induced greater relaxation in segments from old than from young SHR. Electrical field stimulation induced a tritium release in arteries preincubated with [(3)H]-noradrenaline, that was similar in both young and old SHR rats. Electrical field stimulation induced NO(2)(-) formation, which was greater in segments from old than young SHR rats. Basal cGMP levels and those stimulated with sodium nitroprusside were similar in segments from both groups. Superoxide anion production was greater from old than young SHR rats. Peroxynitrite production induced by electrical field stimulation was only detected in segments from old SHR. The results obtained in mesenteric arteries from old SHR showed increased neuronal NO release and superoxide anion production with respect to those observed in arteries from young SHR rats. This induced decreased NO bioavailability through peroxynitrite formation. The final effect is to decrease the involvement of neuronal NO in electrical field stimulation-induced vasomotor response in arteries from old SHR rats.
