Effects Of Hypertension And Pharmacological Intervention On The Left Ventricular Remodeling In The Neuroendocrine Hypertensive Rat

Objective To determine the effect of αl-adrenergic antagonist parzosin, ACE inhibitor cilazapril and tumor necrosis factor-α inhibitor pentoxifylline on left ventricular myocardial matrix collagen remodeling in neuroendocrine hypertensive rat.Methods A neuroendocrine hypertensive model was established with adult Wistar rat (n=34), three groups of neuroendocrine hypertensive rats were treated via stomach perfusion with parzosin (2mg.kg~-1.d~-l)(Hα,n=8), cilazapril (2.5mg.kg~-1.d~-1) (Hace, n=8) or pentoxifylline (100mg.kg~-1.d~-1) (Hptx, n=8). A group of untreated neuroendocrine hypertensive rats was as experimental control one (He, n=10), a group of normotensive Wistar rats was used as normal control (Nc, n=10). After 12 weeks treatments, systemic Blood pressure, heart rate, left ventricular weight were observed. Serum procollagen type m levels, serum tumor necrosis factor-a levels were measured by radioimmuoassay, total collagen volume fraction (TCVF) and CVFs of type I and type III were determined by videodensitometry. Results Systolic pressure, left ventricular weight, serum procollagen type III, serum tumor necrosis factor-a, total collagen volume fraction (TCVF) and CVFs of type I/Ill in group of He were significantly higher than those in the group of Nc ( P<0.05 ) ; systolic pressure, leftventricular weight, CVFs of type I were reduced to the same extent in neuroendocrine hypertensive rats treated with cilazapril or parzosin, however, compared to the control rats, TCVF and CVFs of type III in cilazapril group were much more reduced. Furthermore, cilazapril but not parzosin reduced serum procollagen type III, serum tumor necrosis factor-a. Pentoxifylline could reduce serum procollagen type III, serum tumor necrosis factor-a, CVF, CVFs of type I/III without the reduction of systolic pressure and left ventricular weight.Conclusions (1) Hypertension can lead left ventricular weight increasing and myocardial matrix fibrosis in neuroendocrine hypertensive rats, it suggests that blood pressure increasing is the initial factor of left ventricular hypertrophy and myocardial fibrosis; administration of ACE inhibitor and al-adrenergic antagonist can reduce blood pressure and left ventricular weight, postpone myocardial fibrosis. (2) ACEI is the effective agent to reverse left ventricular hypertrophy and myocardial fibrosis, which can be achieved mostly by the inhibit of ACE, the decrease of Agll synthesis and the increase of kinkin, partially from the reduction of tumor necrosis factor-a. (3) Cytokine such as TNF-a affect developing of myocardial fibrosis, antihypertension drug combining with tumor necrosis factor-a inhibitor pentoxifylline may increase the effect on reversing myocardial fibrosis in neuroendocrine hypertensive rats.