Membrane abnormalities in essential hypertensives (EH) are well known. The respiratory burst enzyme, NADPH oxidase is located in the cell membrane of the neutrophil (PMNLs) and its activity is important in generation of oxygen derived free radical (OFR). Recently OFR have been implicated in vascular changes in variety of conditions. An attempt was made to delineate the status of OFR and antioxidants in EH. Ten, age and sex-matched, healthy controls (GpI) and 26 untreated EH (Gp IIA mild-8, Gp IIB Moderate-8, Gp IIC Severe-10) were studied. After clinical examination and basic laboratory evaluation of subjects, neutrophils isolated from their blood were studied. Chemiluminescence (CL) emitted by PMNLs after stimulation was measured (counts/min) in a luminometer and was taken as measure of OFR production and thereby of NADPH oxidase activity. The levels of antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH), were also estimated. Chemiluminescence was increased significantly (p less than 0.01) in Gp IIC (243.04 +/- 24.9 x 10(3) counts per minute) as compared to Gp IIA (2.80 +/- 1.87), Gp IIB (34.54 +/- 30.24) and Gp I (0.52 +/- 0.15) and SOD was reduced significantly (p less than 0.05) in all EH (Gp IIA 3.9 +/- 0.3 units per mg protein, Gp IIB 3.5 +/- 0.3 and Gp IIC 3.12 +/- 0.3) as compared to controls (4.1 +/- 0.2). Similarly GSH was reduced (p less than 0.05) in EH (Gp IIA 11.2 +/- 1.7 mg per gm protein, Gp IIB 8.5 +/- 1.1 and Gp IIC 6.6 +/- 0.3) as compared to Gp I (13.5 +/- 2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

After peritoneal macrophages had been exposed to different concentrations of nifedipine (10-120 ng mL-1) there was a significant increase (P less than 0.001) in the percentage of Leishmania donovani infected macrophages compared with controls. Parasite load was also significantly increased (P less than 0.001) in nifedipine-treated, L. donovani infected, BALB/c mice, compared with untreated, infected mice, post-inoculation. Peak chemiluminescence responses were significantly depressed (P less than 0.001) in nifedipine-treated infected mice compared with untreated mice post-inoculation. It is suggested that availability of intracellular calcium is a factor in the defense mechanism of inflammatory cells in L. donovani infections.

Administration of nifedipine to mice over a period of six months caused a significant (p < 0.05) decrease in neutrophilic functions viz superoxide generation, coupled to NADPH oxidase activity as well as NADPH production by HMP shunt. Properties like chemotaxis and phagocytosis showed a similar decrease. From this study, it is seen that nifedipine causes neutrophil functional abrogation which is therefore an apparent concern for the prolonged usage of the drug. However, relevance of the mouse model to clinical situation needs further investigation.