CHARACTERIZATION OF ENDOTHELIUM-DERIVED RELAXING FACTOR INVOLVEMENT IN THE POTENTIATING EFFECT OF PARATHYROIDECTOMY ON NOREPINEPHRINE-INDUCED RAT AORTIC CONTRACTION

Previous results have shown that the contractile response to norepinep hrine: (NE) was enhanced in isolated aortae from SHR and normotensive Wistar parathyroidectomized rats. In this work we sought to characteri ze the contribution of endothelium-derived relaxing factor (EDRF) rele ase to this effect which is not linked to hypertension. Parathyroidect omy (PTX) was performed by surgery on 5 week-old male Wistar rats. Fiv e weeks later intact (E+) and rubbed (E-) aortic rings were mounted in an organ chamber for isometric tension recording. KCl-induced contrac tions were potentiated in PTX E+ aortae compared to sham operated (SO) , (P < 0.05), but not in denuded E- aortae. Similarly NE (1 nM- 10 mu M) induced a potentiated contractile response in PTX E+ (P < 0.01), bu t not in PTX E- rings; nevertheless the sensitivity did not change. Af ter removal of endothelium, the expected enhanced contraction and sens itivity observed in SO rats was not present in PTX. The NO synthase in hibitor L-NAME (20 mu M), enhanced sensitivity to NE in SO but not in PTX E+ aortic rings. In addition, hemoglobin (Hb, 10 mu M) enhanced NE contraction in SO (P < 0.01) aortic rings, but to a lesser extent in PTX rat aortae. Moreover, in the presence of L-NAME or Kb, SO and PTX aortae displayed a similar contraction. Superoxide dismutase (SOD, 150 U/ml) diminished the NE contraction since NO was protected from degra dation but the difference was still present between SO and PTX rat aor tae, ruling out the possible implication of superoxide anions in the h yperreactivity of PTX aortae. On the other hand, A23187, which induces EDRF release, reduced the level of NE contraction as expected, but su ppressed the PTX enhancing effect and in calcium-free solution the enh ancement of contraction after PTX was not observed. These experiments extend to the rat the observations previously obtained in rabbit aorta : extracellular calcium is a major determining factor in NO production . Acetylcholine and A23187 (cumulative doses) produced an endothelium- dependent relaxation which was not significantly modified in NE-pre-co ntracted PTX aortae compared to SO aortae. L-arginine (100 mu M), reve rsed the L-NAME inhibitory effect and induced an attenuated endotheliu m-dependent relaxation in PTX vessels (P < 0.01). In conclusion, in ra t isolated aortae the enhancing effect of parathyroidectomy on norepin ephrine and KCI contractions is due to a diminished endothelial nitric oxide production. This might arise via a decrease of the constitutive NO synthase activity in an extracellular calcium-dependent manner.