BLOCKADE OF CALCIUM CHANNELS AND AT1 RECEPTORS PREVENTS THE HYPERTENSIVE EFFECT OF CALCILYTIC NPS 2143 IN RATS

INTRODUCTIONThe presence of the calcium receptor on the cells surface (1)and the discovery of the compounds that might activate (2, 3) orinhibit (4) this receptor created the possibility ofpharmacological correction of parathyroid hormone (PTH)secretion by the parathyroid glands. The agonists of calciumreceptor, calcimimetics, decrease PTH secretion in rats (2, 5) andhumans (6), whereas, the antagonists of the calcium receptor,that were named calcilytics, induced an increase of PTHsecretion in rats (7, 8) and cultured bovine parathyroid cells (4).Experimental studies have repeatedly confirmed the anaboliceffect of exogenous PTH injections on the skeleton (7).Therefore, the calcilytic compounds that inhibit activity ofcalcium receptor and thus stimulate PTH secretion are oftenconsidered as a future way in the treatment of the osteoporoticpatients.Anew observation is the influence of calcilytic NPS 2143 onthe blood pressure in rats. Administration of NPS 2143 resultedin a rise of blood pressure in normotensive rats. Moreover , in ratswith surgically removed parathyroid glands the hypertensiveeffect did not occur (8). The biological mechanism that mediatesthe observed phenomenon is incompletely elucidated.The possibility exists that the calcium receptor dependentsecretion of a hypertensiogenic factors from parathyroidssubsequently af fected the vascular system. Therefore decrease ofcalcium channels and the type 1 angiotensin II (AT1) receptorsactivity might reduce the hypertensive effect of NPS 2143infusion since both of them are present in the cell membrane ofthe vascular smooth muscle cells, their activity influenceintracellular calcium concentration [Ca