Different responses of calcitonin gene-related peptide between losartan and prazosin in early phase of renovascular hypertension

Abstract

Abstract: AIM: To explore the response of calcitonin gene-related peptide (CGRP) in early phase hypertension, and the effect of two kinds of antihypertensive drugs, losartan or prazosin, on the response of CGRP in the process of hypotension.METHODS: The 2-kidney, 1-clip Goldblatt (2k1c) hypertensive rats were used in the present study, the blood pressure was measured by the tail-cuff method under conscious conditions, the mean artery pressure was calculated. The CGRP-like and angiotensin Ⅱ(AngⅡ) immunoactivity in the plasma were measured using radioimmunoassay.The reverse-transcription polymerase chain reaction (RT-PCR) was used for the determination of the expression of CGRP mRNA in the lumbar dorsal root ganglia(DRG).RESULTS: The systolic blood pressure (SBP) and mean artery pressure significantly increased at the tenth day after operation (P<0.01). The plasma levels of CGRP and Ang II(P<0.01, P<0.01) and the expression of CGRP mRNA were significantly increased compared with those in control group (P<0.05) at the end of the experiment.Treatment with losartan significantly decreased the blood pressure and increased the plasma concentrations of AngⅡ and CGRP (P<0.01, P<0.01) and the expression of CGRP mRNA in DRG (P<0.05).However, treatment with prazosin caused a hypotensive effect but companied with the decrease of CGRP in plasma concentration and mRNA in the DRG (P<0.05, P<0.01), and did not significantly increase the plasma Ang Ⅱ(P>0.05) compared with non-treated 2K1C hypertensive rats.CONCLUSION: These results suggest that the Goldblatt 2K1C rats exhibit a compensatory action of sensory nerves.The depressor mechanism of losartan or prazosin may be related to different effects on the synthesis and release of CGRP in the 2K1C Goldblatt hypertensive rats.

Key words: calcitonin gene-related peptide, losartan, prazosin, hypertension

CLC Number:

R965

QIN Xu-ping, CHEN Yun, QIN You-fa, TIAN Hai-hong, SUN Fei. Different responses of calcitonin gene-related peptide between losartan and prazosin in early phase of renovascular hypertension[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 42-47.

References

[1] Kawasaki H, Takasaki K, Saitio A, et al. Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat[J]. Nature, 1988, 335(6186): 164-167.
[2] Kawasaki H, Nuki C, Saito A, et al. Adrenergic modulation of calcitonin gene-related peptide-contailing nervemediated vasodilation in the rat mesenteric resistance vessel[J].Brain Res, 1990, 506(2): 287-290.
[3] Kawasaki H, Nuki C, Saito A, et al. Role of calcitonin gene-related peptide-containing nerves in the vascular adrenergic neurotransmission[J].J Pharmacol Exp Ther,1990, 252(1): 403-409.
[4] Gangula PR, Zhao H, Supowit SC, et al. Increased blood pressure in alpha-calcitonin gene-related peptide calcitonin gene knockout mice[J].Hypertension, 2000, 35(1/2): 470-475.
[5] Kagiyama S, Varela A, Phillips MI, et al. Antisense inhibition of brain reni-angiotensin system decreased blood pressure in chronic 2-kidney, 1 clip hypertensive rats [J].Hypertension, 2001, 3 (2/2): 371-375.
[6] Kawasaki H, Takenaga M, Araki H, et al. Angiotensin inhibits neurotransmission of calcitonin gene-related peptide-containing vasodilater nerves in mesteric artery of spontaneously hypertensive rats [J].J Pharmacol Exp Ther, 1998, 284(2): 508-515.
[7] Kawasaki H.Effects of chronic administration of antihypertensive drugs on vasodilation mediated by calcitonin gene-related peptide-containing vasodilator nerves in spontaneously hypertensive rats[J].Clin Exp Pharmacol Physiol, 1992, 19(8): 569-573.
[8] Qin XP, Ye F, Liao DF, et al. Involvement of CGRP in depressor effect of losartan or perindopril in rats[J].Eur J Pharmacology, 2003, 464(1): 63-67.
[9] Peng J, Lu R, Deng HW, et al. Involvment of α-calcitonin gene-related peptide in monophoshoryl lipid A-induced delayed preconditioning in rat hearts[J].Eur J Pharmocal, 2002, 436(1 2): 89-91.
[10] Wang ZG, Liu JL, Liu Y, et al. Increased plasma vasoactive substances and antioxidant enzymes levels in prehypertensive patients[J].Zhonghua Xin Xue Guan Bing Za Zhi, 2007, 35(8): 719-22.
[11] Wang DH, Wu W, Lookingland KJ.Degeneration of capsaicin-sensitive sensory nerves leads to increase salt sensitive through enhancement of sympathoexcitatory response[J].Hypertension, 2001, 37(2/2): 440-443.
[12] Shi XY, Yang Y, Zhao YT.Plasma calcitonin gene-related peptide level in patients with essential hypertention[J]. Zhonghua Nei Ke Za Zhi, 1990, 29(10): 616-618, 639.
[13] Hobara N, Gessei-Tsutsumi N, Goda M, et al. Long-term inhibition of angiotensin prevents reduction of periarterial innervation of calcitonin gene-related peptide (CGRP)-containing nerves in spontaneously hypertensive rats[J].Hypertens Res, 2005, 28(5): 465-74.
[14] Katki KA, Supowit SC, Dipette DJ.Role of calcitonin gene-related peptide and substance P in Dahl-salt hypertension[J].Hypertension, 2001, 38(3 2): 679-682.
[15] Supowit SC, Gururaj A, Ramana CV, et al. Enhanced neuronal expression of calcitonin gene-related peptide in mineralocoricoid-salt hypertension [J].Hypertension, 1995, 25(6): 1333-1338.
[16] Supowit SC, Zhao H, Hallman DM, et al. Calcitonin gene-related peptides is a depressor of deoxycorticosteronesalt hypertension in the rat[J].Hypertension, 1997, 29(4): 945-950.
[17] Supowit SC, Zhao H, Hallman DM, et al. Calcitonin gene-related peptides is a depressor in subtotal nephrectomy hypertension in the rat[J].Hypertension, 1998, 31: 391-396.
[18] Komine N, Khang S, Wead LM, et al. Effect of combining an ACE inhibitor and an angiotensin II receptor blocker on plasma and kidney tissue angiotensin II levels[J].Am J Kidney Dis, 2002, 39(1): 159-164.