Inducible nitric oxide synthase in spontaneous hypertensive rats: Effects of atrial natriuretic peptide

COSTA A.; ELESGARAY R.; CANIFFI C.; BALASZCZUK A.; ARRANZ C.

Madrid, España

Congreso; Sixteenth European Meeting on Hypertension.; 2006

European Society of Hypertension

In previous studies we have demonstrated that atrial natriuretic peptide (ANP) increased vascular, renal and cardiac nitric oxide synthase (NOS) activity in spontaneously hypertensive rats (SHR). The aim of the present study was to investigate the role of inducible NOS (iNOS) in the effects of ANP on kidney and aorta artery in SHR. Design and Methods: SHR and Wistar Kyoto rats (WKY) were sacrificed and NOS catalytic activity was determined in renal medulla and cortex and aorta by measuring the conversion of L-[U14C]-arginine to L-[U14C]-citrulline, after the addition of: ANP(1 µM), cANP (NPR-C agonist, 1 µM) or aminoguanidine (AG, iNOS inhibitor, 1 µM). SHR and Wistar Kyoto rats (WKY) were sacrificed and NOS catalytic activity was determined in renal medulla and cortex and aorta by measuring the conversion of L-[U14C]-arginine to L-[U14C]-citrulline, after the addition of: ANP(1 µM), cANP (NPR-C agonist, 1 µM) or aminoguanidine (AG, iNOS inhibitor, 1 µM). Results: The results are expressed as percentage(%) of decrease or increase respect to the basal activity of NOS. The results are expressed as percentage(%) of decrease or increase respect to the basal activity of NOS. AG ANP ANP+AG cANP cANP+AG Medulla WKY −13.1±1.4 35.5±5.1 25.2±3.0# 19.8±3.0# 8.8±1.1§ Medulla SHR −18.2±2.1* 25.9±2.1* 13.0±1.1*# 17.9±1.7# 4.9±1.0*§ Cortex WKY −9.6±1.6 43.9±3.4 32.2±3.1# 18.6±2.9# 7.7±1.2§ Cortex SHR −15.7±2.3* 30.0±3.9* 12.9±2.2*# 17.2±2.8# 3.0±0.6*§ Aorta WKY −12.6±1.2 76.9±11.4 63.9±5.9# 18.7±2.5# 5.6±0.5§ Aorta SHR −16.5±1.1* 39.9±5.8* 23.2±2.8*# 19.5±2.0# 8.1±1.0*§ * p < 0.01 vs WKY same treatment; # p < 0.01 vs ANP; § p < 0.01 vs cANP. In all studied tissues, iNOS inhibition diminished basal activity of NOS in both groups, this decrease was higher in SHR than WKY, indicating a higher basal iNOS activity in SHR group. NOS activity induced by ANP in SHR was lower than the observed in WKY. Thus, the increase in NOS activity induced by NPR-C agonist was lower than ANP adding, showing no differences between SHR and WKY. These results suggest an alteration in NOS activation via ANP probably involving NPR-A and/or NPR-B receptors in SHR. In the kidney, iNOS inhibition diminished NOS activity induced by ANP and this decrease was higher than the observed on basal activity in both groups. This fact was not observed with cANP. These results suggest that ANP induced the activation of renal iNOS and this stimulation would be due to the interaction between ANP and NPR-A and/or NPR-B in this model of spontaneous hypertension.