Effects Of Valsartan On The Structure,Function And Pro-EGF MRNA Expression Of Vessels In Spontaneously Hypertensive Rats

Aim: To study the effects of angiotensin receptor antaganist-valsartan on vascular hypertrophy,vasomotion function and aorta vascular smooth muscle cell EGF precursor (pro-EGF) mRNA expression in spontaneously hypertensive rats (SHRs).Methods: 30 tewelve-week-old male SHRs were devided into 3 groups at random: untreated control(water,n=10)(SHRc),low-dose (10mg?kg-1?d-1,n=10) (SHRsv) and high-dose group(30mg?kg-1?d-1,n=10) (SHRlv). Angiotensin receptor antaganist-valsartan were given by gavage. Age-matched WKY(n=10) were given only some water as control. Systolic blood pressure(SBP) was measured before treatment and after four-week-treatment. Wall-to-lumen area ratio(W/L) of thoracic aorta and third grade branch of mesenteric artery were assessed by morphormetric assay.The effects of valsartan on vascular reactivity to vasoactive substances were studied with rings of thoracic aorta and mesenteric artery isolated from rats. By the cell culture,we studied the effects of AngII on VSMC proliferation and DNA synthesis of SHR and WKY and the effects of valsartan on VSMC proliferation and DNA synthesis of SHR and WKY induced by AngII. The effects of valsartan on VSMC pro-EGF mRNA expression were measured by RT-PCR.Results: Before experiment,SBP of SHRc were higher than WKY,but there were not different among SBP of SHRc,SHRsv and SHRlv. After 4 weeks , SBP of SHRc were higher than WKY(p<0.01). SBP of SHRsv and SHRlv were significantly lower than SHRc (p<0.01),expecially in the SHRlv. W/L of thoracic aorta and third grade branch of mesenteric artery in SHRc were higher than WKY(p<0.01).Compared with SHRc , W/L of third grade branch of mesenteric artery in SHRsv and SHRlv were significantly lower (p<0.01) . W/L of thoracic aorta was decreased in SHRlv (p<0.01) ,but not in SHRsv (p>0.05). The relaxation sensitivity to SNP was increased and the contraction sensitivity to NE was depressed after 4-week treatment in both of the two arteries. AngII(10-5-10-8M)exhibited a proliferation-promoting effect on the increases in VSMCs number and 3H-TdR incorporation.The increased VSMCs number and 3H-TdR incorporation induced by AngII(10-6M) were inhibited by valsartan(10-5-10-8M) in a concentration-dependent manner. Pro-EGF mRNA expression only in cultured SHR VSMC , not in the cultured VSMC of WKY. Valsartan dose-dependently depressed Pro-EGF mRNA expression level of cultured SHR VSMC (p<0.01) . Compared with SHRc , after 4 weeks, Pro-EGF mRNA expression level of SHRsv and SHRlv VSMC were significant lower.Conclusions: Valsartan decrease SBP of SHR, inhibit SHR VSMC proliferation, reverse vascular hypertrophy of thoracic aorta and mesenteric artery in SHR, improve the two arteries vasomotion function. Pro-EGF mRNA expression only in SHR VSMC, not in the VSMC of WKY. It indicated pro-EGF gene may play an important role in hypertension advance . Valsartan depressed SHR VSMC pro-EGF mRNA expression.