Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1 receptor effects on renal bradykinin and cGMP.

Angiotensin (Ang) receptor blockers (ARBs) increase bradykinin (BK) by antagonizing Ang II at its type 1 (AT(1)) receptors and diverting Ang II to its counterregulatory type 2 (AT(2)) receptors. Because the effect of ARBs on BK is constrained by the short half-life of BK and because ACE inhibitors block the degradation of BK, this study was designed to test the hypothesis that an ACE inhibitor can potentiate ARB-induced increases in renal interstitial fluid (RIF) BK levels. We used a microdialysis technique to recover BK and cGMP in vivo from the RIF of sodium-depleted, conscious Sprague-Dawley rats infused for 60 minutes with the AT(1) receptor blocker valsartan (0.17 mg/kg per minute), with the active metabolite of the ACE inhibitor benazepril (benazeprilate, 0.05 mg/kg per minute), or with the specific AT(2) receptor blocker PD 123,319 (50 microg/kg per minute) alone or combined. Each animal served as its own control. RIF BK and cGMP levels increased significantly over 1 hour in response to valsartan, benazeprilate, or both but not to a vehicle control (P<0.01). The combined benazeprilate-valsartan effect was greater than the sum of their individual effects, suggesting potentiation rather than addition, and was abolished by PD 123,319. We demonstrate for the first time that an ACE inhibitor (benazepril) and an ARB (valsartan) potentiate each other, and we postulate that such combinations may be beneficial in clinical states marked by Ang II elevation, such as chronic heart failure, postinfarction left ventricular dysfunction, and hypertension.

Correlation of actinomycin X2 to the lipid profile in static and shaken cultures of Streptomyces nasri strain YG62.

Streptomyces nasri strain YG62 produces a broad-spectrum antibiotic designated actinomycin X2. The influence of static and shaken incubation on the production of actinomycin X2 and lipid profiles of S. nasri strain YG62 was investigated. It was found that shaken incubation was superior to the static process for both actinomycin X2 (2-fold) and total lipids (1.6-fold). Triglyceride and phospholipid levels paralleled the actinomycin X2 production with an increase in the triglyceride (2.8-fold) and phospholipid (1.2-fold) concentrations in the shaken culture over the static incubation. Analysis of fatty acid patterns revealed the occurrence of a wide range of fatty acids (C10-C22). The mean percentage of total saturated fatty acids in shaken culture was higher than those of the static culture. The mean percentage of mono-unsaturated fatty acids was almost the same in both cultures. The mean percentage of the total polyunsaturated fatty acids in the static culture was slightly higher than that of the shaken culture. The polyunsaturated/saturated fatty acid ratio (P/S) was higher in the static culture compared with the shaken culture. A positive correlation was recorded between triglycerides, phospholipids and actinomycin X2. A negative correlation on the other hand, was found between fatty acids and actinomycin X2.

Circulating growth hormone, insulin-like growth factor I, cortisol and free thyroxine in children with schistosomiasis with and without hepatic fibrosis.

Serum insulin, growth hormone (GH), cortisol, free thyroxine (T4) and plasma insulin-like growth factor I(IGF-I) concentrations were measured in 20 children suffering from schistosomiasis as well as 10 healthy age-matched controls. Circulating GH and insulin levels were determined after an intravenous infusion of arginine HCl (10 per cent solution, 0.5 g/kg). Children with schistosomal hepatic fibrosis (n = 10) had heights more than 2 SD below the mean for their age and sex. Their circulating IGF-I, free T4, and cortisol levels were significantly reduced. They had markedly elevated serum insulin concentrations with normal response to arginine infusion. Their basal GH levels were normal with significantly reduced GH response to arginine provocation. Compared to controls, they had significantly lower serum albumin concentrations, prolonged prothrombin time and elevated alanine transferase (ALT) levels. Free T4 and IGF-I concentrations, and GH increments after provocation correlated significantly with the percentile heights of these patients (r = 0.90, 0.70, and 0.83, P less than or equal to 0.001, less than or equal to 0.05 and less than or equal to 0.01 respectively). Their IGF-I levels correlated closely with the prothrombin time and ALT concentrations (r = 0.87 and 0.77, P less than or equal to 0.002 and less than or equal to 0.01, respectively). It is suggested that the depressed circulating IGF-I and free T4 levels in addition to deficient GH reserve may be responsible for stunted stature in patients with schistosomal hepatic fibrosis.