THE RECEPTOR OCCUPATION AND PLASMA-CONCENTRATION OF NKY-722, A WATER-SOLUBLE DIHYDROPYRIDINE-TYPE CALCIUM-ANTAGONIST, IN SPONTANEOUSLY HYPERTENSIVE RATS

1 The occupation in vivo by NKY-722 of 1,4-dihydropyridine (DHP) calci um antagonist receptors in myocardium, aorta and cerebral cortex was i nvestigated. At 1 and 3 h after oral administration of NKY-722 (3 mg k g(-1)) in spontaneously hypertensive rats (SHR), there was a significa nt (44 and 41%, respectively) decrease in the number of myocardial (+) -[H-3]-PN 200-110 binding sites (B-max) compared to control values. A greater reduction of B-max values was observed at 1 (86%), 3 (88%), 6 (63%) and 12 (46%) h later by a higher dose (10 mg kg(-1)) of this dru g. The occupation of myocardial 1,4-DHP calcium antagonist receptors a fter oral administration of NKY-722 correlated significantly with its plasma concentration. There was a significant decrease in cerebral cor tical (+)-[H-3]-PN 200-110 binding (B-max) at 1 and 3 h after oral adm inistration of NKY-722 (10 mg kg(-1)). 2 Oral administration of nicard ipine (10 mg kg(-1)) in SHR caused a significant reduction of B-max va lues for (+)-[H-3]-PN 200-110 binding in myocardium at 1 and 3 h later and in cerebral cortex at 1 h later. 3 The in vivo specific binding o f(+)-[H-3]-PN 200-110 in particulate fractions of aorta of SHR was sig nificantly (79 and 83%, respectively) reduced at 1 and 6 h after oral administration of NKY-722 (3 mg kg(-1)), while myocardial (+)-[H-3]-PN 200-110 binding was decreased by 52% only at 1 h later. Also, nicardi pine administration reduced in vivo (+)-[H-3]-PN 200-110 binding in ao rta at 1 and 6 h later and in myocardium at 1 h later. On the other ha nd, the administration of both NKY-722 and nicardipine had no signific ant effect on in vivo (+)-[H-3]-PN 200-110 binding in cerebreal cortex . 4 It is concluded that NKY-722 may exert more selective and sustaine d occupation in vivo of 1,4-DHP calcium antagonist receptors in vascul ar tissues of SHR than in myocardial and brain tissues.