Effects of C-type natriuretic peptide on vascular reactivity in hypertension. Participation of nitric oxide system and potassium channels

COSTA MARÍA DE LOS ÁNGELES; CANIFFI CAROLINA; SUEIRO LAURA; CERNIELLO MICAELA; SUÁREZ DI SALVO DAIANA; MENDES GARRIDO FACUNDO; WENK GRETEL; ARRANZ CRISTINA

Londres

Congreso; 22nd European Meeting of Hypertension.; 2012

European Society of Hypertension.

The aim was to study the mechanisms involved in vascular relaxation induced by CNP and NO system participation in spontaneously hypertensive rats (SHR). Methods: Aorta segments of 3–5 mm from Wistar (W) and SHR, were sus- pended in Krebs solution (37°C, gassed 95% O2-5% CO2, pH: 7.4). The aortic rings were allowed to equilibrate for 60 min and readjusted to basal tension 1 g. Isometric tension (g) was recorded by a force-transducer, in presence of: phenylephrine (PE, 10-7-10-5 M), CNP (10-12-10-6 M), L-NAME (NOS inhibitor, 10−5 M), indomethacin (Indo, cyclooxygenase inhibitor, 10−5 M) and tetraethylammonium (TEA, non selective K+ channel blocker, 1 mM) and/or in absence of endothelium (NoE). Endothelium integrity was verified with acetylcholine. Aortic NOS activity (pmol 14C L-citrulline/g tissue·min) was determined. Results: NOS activity was higher in SHR, and CNP increases NOS activity in both groups (W-basal: 202 ± 5; W-CNP: 315 ± 9*; SHR-basal: 356 ± 9*; SHR-CNP: 432 ± 10# ; *p < 0.01 vs. W-basal, # p < 0.01 vs. SHR-basal) but the increase in SHR was lower than W (W(CNP-basal) = 113 ± 4 vs. SHR(CNP-basal) = 76 ± 6; p < 0.01; n = 8 rats/group). NOS blockade with L-NAME diminished basal NOS activity and revert CNP effects (data not shown). ANOVA followed by Bonferroni’s post hoc test. Table: Maximal relaxation(Rmax) and concentration of the CNP (expressed as negative log molar) producing 50% of maximum relaxation(pEC50). Rmax pEC50 W CNP 82.20±4.03 8.09±0.19 L-NAME+CNP 59.81±5.83* 6.08±0.03‡ NoE+CNP 67.69±9.90 6.21±0.04‡ Indo+CNP 75.39±4.99 7.61±0.12 SHR CNP 81.60±4.16 7.06±0.10‡ L-NAME+CNP 50.58±6.68^ 5.87±0.22† NoE+CNP 61.72±8.64^ 6.10±0.12† Indo+CNP 83.33±6.65 8.41±0.16† In rings with endothelium the maximal response was similar in W and SHR at the highest concentration of CNP but the pEC50 of CNP was lower in SHR. NOS blockade diminished relaxant response to CNP in PE pre-constricted rings of both groups. On the other hand, although indomethacin did not significantly affect maximal CNP-induced relaxation, in SHR diminished pEC50. Pre-incubation with TEA of rings denuded of endothelium abolished both arterial relaxation (W=15.79±7.75*; SHR=7.57±4.00^) and pEC50 of CNP in aortic rings of W and SHR. *p