Down-regulation of cardiac bradykinin B2 receptors and eNOs mRNA in rats with remnant kidneys

Abstract

The changes in the expression of cardiac bradykinin B2 receptors (BKB2Rs) and endogenous nitrix oxide synthase (eNOs) mRNA were studied in rats with remnant kidneys. Thirty-two rats were divided into sham-operated and experimental groups randomly (n=16 in each group). The remnant kidney model was established by 2-stage 5/6 nephrectomy. Blood pressure and serum Cr were measured before operation and 15, 30, 60, 120 days after 5/6 nephrectomy. Eight animals in each group were killed at the first month and 4th month after the operation. The expression of BKB2Rs and eNOs mRNAs was detected by using RT-real time PCR from isolated left ventricle, and their correlation was also analyzed. The results showed that blood pressure and serum Cr were increased significantly 15 days after 5/6 nephrectomy (bothP<0.01), and the hypertension and azomia existed constantly till 120 days but had no significant fluctuation. Cardiac BKB2Rs and eNOs mRNA was declined time-dependently (bothP<0.05). And there was a close positive correlation between cardiac BKB2Rs and eNOs mRNA (r=0.82,P<0.01). It was suggested that a significant chronic renal failure can be produced at least 15 days after 5/6 nephrotomy and can sustain more than 4 months. The expression of BKB2Rs and eNOs was down-regulated time-dependently in this model, and there was a significant correlation between them.

Keywords

bradykinin B2 receptors / endogenous nitric oxide synthase / myocardium / 5/6 nephretomy

References

[1] MarceauF, HessJ F, BachvarovD R. The B1 receptors for kinins. Pharmacol Rev, 1998, 50: 357-357

[2] BhoolaK D, FigueroaC D, WorthyK. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev, 1992, 44: 1-1

[3] NollyH, CarbiniL A, ScicliG, et al.. A local kallikrein-kinin system is present in rat hearts. Hypertension, 1994, 23: 919-919

[4] Hinojosa-LabordeC, FrolichB, CowleyA W. Whole body autoregulation in reduced renal mass hypertension. Hypertension, 1992, 20: 659-659

[5] YayamaK, MatsuokaS, NagaokaM, et al.. Down-regulation of bradykinin B2-receptor mRNA in the heart in pressure-overload cardiac hypertrophy in the rat. Biochem Pharmacol, 2003, 65(5): 1017-1017

[6] BoginE, MassryS G, HararyI. Effect of parathyroid hormone on rat heart cells. J Clin Invest, 1981, 67(4): 1215-1215

[7] TanY, HutchisonF N, JaffaA A. Mechanisms of angiotensin II-induced expression of B2 kinin receptors. J Physiol Heart Circ Physiol, 2004, 286(3): H926-H926

[8] RitterO, SchuhK, BredeM, et al.. AT2 receptor activation regulates myocardial eNOS expression via the calcineurin-NF-AT pathway. FASEB J, 2003, 17(2): 283-283

[9] DowneyJ M. The cellular mechanisms of ischeamic and pharmacological preconditioning. Cardiovasc J S Afr, 2004, 15(Suppl 1): 3-3