Experimental Study On Changes Of Pathologic Ultrastructure Endothelia Function And The Activity Of Fibrinoysis Of Shr And Drugs Intervention

Objectives: To investigate changes of the blood pressure, the function of endothelium (NO, NOS), the activity of fibrinolysis, the microstructure and ultrastructure of the target organs in spontaneously hypertensive rats(SHR) by animal experiment; To observe the effect of antihypertensive drugs and anti-oxidation agents on the blood pressure ,the function of endothelium(NO, NOS),the activity of fibrinolysis and the protective function on the microstructure and ultrastructure of the target organs in SHR. To supply experimental evidences for prevention of complications of cerebrovascular and cardiovascular diseases, so to guide clinical drug administration.Material and Methods: Forty-eight 12-weeks old male SHRs were randomized into six groups (each group, n=8), who were fed respectively with irbesartan (10mg/kg.d), imidarpril(5mg/kg.d), amlodipine(5mg/kg.d), carvedilol (30mg/kg.d), probucol(10mg/kg.d), NS(10mg/kg.d) for 8 weeks. Eight age-matched male wistar-kyoto rats (WKY) were used as controls and fed with NS(10mg/kg.d) for 8 weeks. The blood pressure and the heart rate were measured by RBP-1 type rat tail-cuff monitor. Three milliliters of blood were collected at venous angle simultaneously. The plasma and the serum were collected after centrifugation. The technique of nitrate reductase was used to measure the activity of NO , NOS, and chromogenic substrate assay for t-PA and PAI-1. At the end of the experiment, each group of the rats were injected with 10% chloral hydrate into abdominal cavity after weighted. The left ventricule(including the ventricular septum ) and the right ventricule were weighted after thoracotomy. Then the left and right ventricular weight index (LVW/BW), (RVW/BW) were calculated. The microstructure and the ultrastructure of the brain, myocardium, blood vessel of artery, and the kidney were observed by light microscope and electron microscopy.Result:The values of blood pressure, heart rate, plasma PAI-1 were much greater in SHR groups than those in WKY group (P<0.01-0.001). But the levels of serum NO, NOS, plasma t-PA in SHR were significantly lower than those in WKY group(P<0.001). The levels of blood pressure were lowered after treatment in irbesartan imidaprih amlodipine> carvedilol groups except the probucol one(P<0.001). The change of heart rate was not significant after treatment in irbesartan > imidapril >amlodipine> and probucol groups(P>0.05), but the heart rate in carvedilol group were much lower than before(P<0.01). The levels of serum NO, NOS(P<0.001) and the activity of serum PAI-1 (P<0.001) were significantly decreased after being treated with irbesartan ? imidaprih amlodipine^ carvedilol and probucol. Level of plasma t-PA after treatment in irbesartan, imidapril and amlodipine groups were much higher than before. The level of plasma t-PA was not changed after treatment in probucol and carvedilol groups (P>0.05). The left ventricular weight, the left and right ventricular weight index of SHR were higher than those of WKY (PO.01). The left ventricular weight, the left and right ventricular weight index treated with irbesartan imidaprik amlodipine n carvedilol and probucol, especially the groups treated with irbesartan and imidapril were much lower than before.Under the transmission electron microscope , the myocardial cells of SHR control showed that: myocardial cells were hypertrophic, more myofilament were dissolved ,the arrangement of myocardial cells and myofibril were apparently turbulent, part Z thread disappeared; mitochondria assembly was hyperplastic, some mitochondria were swelling ^ some cavitated^ or ridgedisappeared; the shape of nucleolus was aberrant chromatin was sparse > the double deck structure of part kayotheca vanished. In the groups administrated with amlodipine> carvedilol and probucol, it appeared that the arrangement of myofibril was turbulent , mitochondria was swelling but the ridge was clear; nucleolus was lightly karyopyknotic, but the two-layer structure of kayotheca was clear; In the groups administered with irbesartan and imidarpril, it showed that the arrangement of myocardial cells and myofibril were in order, mitochomdria was gently swelling and the two-layer structure was clear too, nucleolus and the distributing of chromatin were normal, kayotheca were clear, Z thread and the structure of capillary vessel were in gear. Under the transmission electron microscope, the endothelial cells of brain basilar artery showed that in the control group, the intima of the blood vessel was ruptured in certain position, endothelial cells were out of hand, cracked cellular remnant and dissociated foam cell appeared on the surface of some cells, some survived endothelia cells became round compound with karyopyknotic ^ chromatin loosens density decreased, and vesicle and compact fat drop could be seen in the cytoplasm, the fundus membrane was not continued, collagens and elastic fibers were ruptured with disordered distribution. In the groups administered with amlodipine, probucol and carvedilol, the damages of endothelial cells were relatively slight, although swelling of the endothelial cells, vacuole in the cytoplasm still developed, the fat drop was decreased significantly; the shape of nucleolus was approximately normal and the fundus membrane was relatively integrated. In the groups administrated with irbesartan and imidarpril, the endothelial cells were integrated and emerged as long fusiform, the nucleolus was flat oval shape and paralleled with cellular long axis, the karyotheca was clear, the chromatin was compact, natural mitochondria > endoplasmic reticulum etc could be seen in the cytoplasm, the fundus membrane was integrated. There were no significant differences between the two groups. The changes of ultrastructure in the SHR renal showed that: in the control group of SHR, the...