ABSTRACT
It has been proposed that renin angiotensin system [RAS] plays a pivotal and perhaps obligatory role in the initiation and progression of ventricular hypertrophy. Glucose and insulin level are associated with left ventricular mass [LVM] in insulin resistant individuals. Antihypertensive drugs always have ditferent effects on glucose insulin levels, RAS and on LVM. To evaluate whether the effect of antihypertensives [Losartan or Ramipril] on LVM are associated with its effects on plasma glucose, insulin and aldosterone we compared their effects on these parameters in a group of insulin resistant, obese hypertensive patients. A total of 20 obese, non diabetic hypertensives who were 45 +/- 4 years had a body mass index of 31.5 +/- 2.5 Kg/m2, were free of coronary or valvular heart disease and had normal left ventricular [LV] function were randomized to treatment with losartan , 50mg daily [n=10]or ramipril 5 mg daily [n=10]. Echocardiograpic left ventricular mass [LVM] corrected for height [LVM/height] and plasma aldosterone [PA] were measured after 4 weeks of washout and 6 months of treatment. Baseline characteristics were similar in both groups. Losartan and ramipril effectively reduced blood pressure while both did not affect significantly fasting plasma glucose or insulin levels. Both ramipril and losartan significantly reduced LVM/ height. In obese hypertensive individuals adequate and similar blood pressure control was achieved with losartan and ramipril, also, in obese hypertensive patients both losartan and ramipril led to a significant regression of left ventricular mass associated with significant decreased plasma aldosterone level
ABSTRACT
This study was designed to examine the effects of combined administration of the angiotensin receptor blocker [AT1RB], valsartan and the angiotensin converting enzyme inhibitor [ACEI], ramipril on renal function in rats with liver cirrhosis. This animal model was induced by giving gradually increased intra-gastric doses of carbon tetrachloride [CCI4]. Thirty male albino rats weighing 150-200 grams were used through this study. Rats were divided as the following: Group [I]: formed of 6 non-cirrhotic control rats. Group [II]: comprised 6 cirrhotic ascitic control rats. Group [III]: Cirrhotic ascitic rats treated with ramipril in a dose of 2.5mg/kg/day for 2 weeks. Group [IV]: Cirrhotic ascitic rats treated with valsartan in a dose of 20mg/kg/day for 2 weeks. Group [V]: Cirrhotic ascitic rats treated with ramipril and valsartan combination for 2 weeks. Daily urine volume and body weight were assessed to follow up the development and progress of ascites. Urinary and plasma sodium and potassium were measured. in addition plasma renin activity [PRA] and serum creatinine were estimated. in cirrhotic ascitic rats combination therapy with ramipril and valsartan was more efficacious than either monotherapy in improving kidney function and salt and water retention. Ramipril is as equally effective as valsartan at ameliorating the decline in renal function and salt a water retention. These results indicate that in rats with liver cirrhosis and ascites, the reno protective effect afforded by combined RAS [renin- angiotensin system] blockade in this model adds further support to the involvement of a tissue based RAS. Although the present study reveals elevation in PRA either in association with monotherapy or combined therapy, RAS blockade improved renal function which indicating that a local RAS confers renoprotective effect. The enhancing effects of ramipril and vaisartan combination on renal electrolyte and volume excretion may reduce the need for diuretics and thus attenuates the risk of their induced electrolyte disturbances
ABSTRACT
Hepatic ischemia is an important factor in the development of hepatic degeneration and necrosis in different hepatic pathological conditions. This study was conducted to declare the effect of pretreatment of albino rats with dihydropyridine L-type calcium channel blockers [nifedipine and amlodipine] on hepatic ischemia reperfusion [l/R]. Furthermore this study investigated the effect oi IIR on plasma levels of endothelin-1 [ET-1] and nitric oxide [NO] and their pathophysiologic links to maintenance of hepatic function. This study was carried on 36 male albino rats. The animals were divide into 6 equal groups, each consisted of 6 rats. Group [1]: sham operated [rats subjected to anesthesia and laparotomy]. Group [II]: control l/R rats, pre-treated with saline. Group [ill]: treated with nifedipine [2mg/kg/day] intré-gasttic for 6 weeks before exposure to sham operation. Group [IV]: l/R treated with nitedipine with the same previously mentioned dose and for the same duration before induction of VR. Group [V]: amlodipine pretreated [0.5mg/kg/day] for 6 weeks, intragastrically and then exposed to sham operation. Group [VI]: received amlodipine 0.5mg/kg/day for 6 weeks before being subjected to I/R. Transient hepatic ischemia for 90 minutes was done under anesthesia by hepatic vascular pedicle clamping followed by 30 minutes reperfusion. Hepatic cell function was tested by measuring plasma alanine transferase [ALT]. This Is In addition to measurements of hepatic tissue calcium content, plasma endothelin-l and plasma nitrites. It was found that UR produced a significant increase in plasma ALT. ET-1, nitrites and hepatic tissue calcium. Both nifedipine and amlodipine induced hepato-protective effect confirmed by prevention of the elevation in plasma levels of ALT and hepatic tissue calcium load. Each of nifedipine and amlodipine had equally prevented the hepatic accumulation of calcium. In spite of this equieffective protection any of the drugs exerted significant changes in plasma ET-1 levels. While plasma nitrites levels remained high. Further studies of these results on hepatic patients are recommended especially in patients given nifedipine or amlodipine for associated cardiovascular problems
ABSTRACT
The present work was conducted to determine the possible in vivo effect of combined administration of losartan [selective angiotensin receptor antagonist; AT1] and spironolactone [aldosterone receptor antagonist] in experimentally induced liver cirrhosis and ascites in rats. Cirrhosis was induced by using carbon tetrachloride [CCl4]. Thirty rats were used throughout this study [6 rats were non-cirrhotic controland24 cirrhotic rats]. Cirrhotic rats were further divided into 4 equal groups as following Group [A]: served as a cirrhotic non-treated control; Group [B]; com- posed of cirrhotic rats treated with losartan 10mg/kg/day for 2 weeks; in tragastrically; Group [C]: comprised cirrhotic rats treated with spironolactone tone 18mg/kg/day for 2 weeks tragastrically; Group [D]: cirrhotic rats treated with combination of both losartan and spironolactone in the previously mentioned dose and duration. Daily urine volume and body weight were assessed throughout the experiment to follow up progress of ascites. Furthermore urinary sodium and potassium were assayed in addition to measurement of plasma sodium, potassium, plasma renin activity [PRA] and plasma aldosterone levels [PA]. Administration of losartan to cirrhotic rats with ascites produced cant reduction in body weight and plasma aldosterone levels associated with a significant increase in urine output with increased sodium excretion. Furthermore losartan treatment induced a significant increase in both plasma potassium and plasma renin activity as compared to cirrhotic non- treated rats. Administration of spironolactone to cirrhotic rats with ascites induced a significant reduction in body weight, urinary potassium excretion and plasma aldosterone levels; but it produced a significant increase in plasma potassium, urine volume and PRA as com- pared to cirrhotic non-treated rats. Cirrhotic ascetic rats received combination of losartan and spironolactone showed additive decrease in body weight, urinary potassium excretion, plasma sodium levels and PA levels. In contrast this combined therapy induced a significant increase in urinary volume, urinary sodium excretion and plasma renin activity. These results thus indicated that combined administration of losartan and spironolactone in rats with liver cirrhosis and ascites had a marked effect on renal electrolytes and volume regulation. These findings suggest the beneficial effects of losartan and spironolactone combination in liver cirrhosis and ascites