| Renin-angiotensin system (RAS) have been shown to play pivotal roles in the development of blood pressure, angiotensin II (Ang II) , besides regulating vascular smooth muscle tone, has properties of growth factors which induces cell hyperplasia or hypertrophy, via over expression of original cancer genes, resulting in cardiac or vascular remodeling.Calcitonin gene-related peptide (CGRP), a 37-amino acid peptide, is distributed widely in vascular tissues of both the central nervous system and the periphery. CGRP is a potent vasculator and plays an important role in modulation of the total peripheral resistance of the systemic circulation through reflex mechanisms. Recently, it has been shown that CGRP concentration in the plasma is decreased in patients with essential hypertension and in spontaneously hypertensive rats, suggesting that the alteration in the level of CGRP may be related to the development ofhypertension. However, the expression of CGRP varies considerably in different animal models of hypertension. To our knowledge, the hypothesis of capsaicin-sensitive sensory nerves has not yet been tested in the 2-kidneys, 1-clip (2K1C, Goldblatt) hypertensive model.In the present studies, therefore, we examined whether the depressor effects of perindopril and losartan are involved in endogenous CGRP in 2K1C Goldblatt rats.METHODSThe Sprague-Dawley rats (220-250g) were anesthetized with sodium Phenobarbital (60mg/kg, i.p.). The left renal artery was separated and clipped with a 0.3 mm silver clip. The control group underwent the same procedure, but without clipping the renal artery. At the end of the fourth, week, the rats were treatment with losartan (20mg/kg) or perindopril (3mg/kg) for 6 weeks. Systolic blood pressure was recorded, once a week, using the tail-cuff method. Concentration of Ang II and CGRP and the activity of renin in the plasma were measured by radioimmunoassay methods. The expression of CGRP mRNA in DRG was determined by RT-PCR. The ratio of heart and body was calculated. Aortic and mesenteric arteries were prepared with methylaldehyde, and the color slides of these tissues stained with hematoxylin and eosin were analyzed using the software of higher clear graphic assay system.RESULTSIn the 2K1C rats, systolic blood pressure and mean artery pressure were significantly raised compared with control group (p<0.01), and the level of CGRP was raised in plasma (p<0.05). A state of thickening in aortas or remodeling mesnenteric arteries was shown in hypertensive rats. Treatment with losartan or perindopril significantly decreased the blood pressure, concomitantly with an increased the plasma concentration of CGRP and the expression of α -CGRP mRNA in dorsal root ganglia. Losartan or peridopril treatment significantly decreased the thickening or remodeling in vascular tissues and diminished radio of heart to body. In the losartan or peridopril-treatment group, the plasma level of Ang II and the plasma activity of rennin were increased.CONCLUSIONS1. The 2K1C Goldblatt model exhibits a compensatory increase of sensory nerve actions.2. The depressor effects and the regressive effect of vascular remodeling of losartan or prindopril may be related stimulation of the synthesis and release of CGRP in the 2K1C Goldblatt hypertensive rats.
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