ENDOTHELIUM-DEPENDENT RELAXATION IN RESISTANCE ARTERIES FROM SPONTANEOUSLY HYPERTENSIVE RATS - EFFECT OF LONG-TERM TREATMENT WITH PERINDOPRIL, QUINAPRIL, HYDRALAZINE OR AMLODIPINE

Objective To examine the effects of different types of antihypertensiv e treatment on endothelium-dependent relaxation in resistance arteries from spontaneously hypertensive rats (SHRs). Design and methods Three -week-old SHRs were treated with the angiotensin converting enzyme (AC E) inhibitor perindopril (1 mg/kg/day) or quinapril (3 mg/kg/day) or t he vasodilator hydralazine (50 mg/kg/day) or the calcium antagonist am lodipine (10 mg/kg/day). Control SHRs and Wistar-Kyoto (WKY) rats were treated with water. After 21 weeks rats were culled and mesenteric re sistance arteries were mounted in a myograph. Relaxation responses to the endothelium-dependent vasodilators acetylcholine (ACh) and bradyki nin were recorded before and after incubation with the nitric oxide sy nthase inhibitor N-G-nitro-L-arginine (L-NOARG), as was the relaxation response to the nitric oxide donor sodium nitroprusside (SNP). Result s All drugs prevented the rise in blood pressure found in the untreate d SHRs. ACh-induced relaxation was significantly impaired in the untre ated SHRs compared with the WKY rats. Treatment with either ACE inhibi tor prevented the development of this impaired response. ACE inhibitor treatment significantly increased the relaxation response to bradykin in. Despite lowering blood pressure,hydralazine or amlodipine had no e ffect on ACh- or bradykinin-induced relaxation. Responses to SNP were not different between untreated SHRs and WKY rats and were not affecte d by drug treatment. Conclusion Specific properties of certain antihyp ertensive drugs may play an important role in restoring endothelium-de pendent relaxation in the small arteries that regulate peripheral resi stance in the SHR.