Φαρμακογενείς μεταβολές των ενδοκυττάριων ηλεκτρολυτών και ιστική ευαισθησία στην ινσουλίνη σε υπερτασικούς ασθενείς

Abstract

Primary hypertension is a multifactorial disease and abnormalities in homeostasis of sodium, potasium, calcium and magnesium in the intracellular enviroment have been incriminated in its etiopathogenesis. Recently many studies have shown that the majority of hypertensive patients have insulin resistance in their peripheral tissues. Insulin resistance causes reduced activity of many transmembranic systems of transportation of electrolytes, and as a consequence leads to increase peripheral vascular resistance. Treatment of primary hypertension leads to considerable improvement of morbididty and mortality from lesions to organ-targets, coronaty events, heart and renal failure and stroke. Many of the antihypertensive drugs in current use have side effects that reduce the benefits from their use. The most recent and most frequently in use classes of antihypertensive drugs are calcium blockers and ACE inhibitors. In this report we examined the effects in the treatment of primary hypertension and in the tissue sensitivity in insulin in the mhomeostasis of sodium, potasium, calcium and magnesium of two representitive drugs of these classes, amlodipine and fosinoprile. Analysis of the results has shown that: 1. Both antihypertensive drugs in use were able to control hypertension in their usual dose for 24 hours. 2. There were no undesirable metabolic effects in the measured hematological and biochemical parameters. In the group of fosinopril, indeed, there was considerable reduction of fibrinogen (p=0.0005). 3. Their effect on lipids was either neutral or posoistive. Specifically, fosinopril caused siglificant increase of apo A (p=0.002) and reduction of LDL-cholesterol (p=0.03), while amlodipine caused significant reduction of triglycerides (p=0.0006) and LDL-cholesterol (p=0.03) and increase of apo A (p=0.01). 109 4. There was no negative effect on renal function, while both drugs caused natriuresis. 5. The levels of serum electrolytes, as sodium, potasium, calcium, pagnesium and phosphorus did not change significantly. 6. Both drugs caused significant improvement in the intracellular electrolytes after two months of treatment. In the group of fosinopril there was significant reduction of intracellular levels of sodium (p=0.002) and calcium (p=0.001) in basal time 0 min, while the itracellular level of potasium and magnesium inncreased although not significantly. In the amlodipine group, the improvement in the intracellular ionic environment also was significant, as there was reductions in the levels of intracellular sodium (p=0.002), and calcium (p=0.01), while there was significant increase of intracellular magnesium (p=0.02) and non significant of potasium (p=0.5), in basal time 0 min and in time 120 min of OGTT. 7. Insulin sensitivity, in the fosinopril group, after 2 months of treatment, improved significantly during the whole duration of OGTT (p0?= 0.0003), p60?=0.00008), p120?=0.003). In amlodipine group improvement was significant only in time 120 min (p=0.0002), while in time 0 and 60 min was not significant. Concluding the two drugs used in our study for the treatment of primary hypertension are effective taken once per day, without significant undesirable clinical and laboratory side effects. The reduction of blood pressure was acompanied by improvement of tissue sensitivity in insulin, while there was improvement in certain lipid indices. Concerning itracellular ionic environment, both drugs caused significant improvement of sodium and calcium and less of potasium and magnesium. This improvement is due, probably, in the normalization of the function of the transmembranic systems of transportation of corresponding ions.