RELEASE OF INTRACELLULAR STORED CALCIUM C AUSES VASOCONSTRICTION IN PRIMARY HYPERTENSION

The effects of specific inhibition of sarcoplasmic Ca2+-ATPase by natu rally occurring sesquiterpene lactone, thapsigargin, on the vasoconstr iction was investigated in aorta from spontaneously hypertensive rats from the Munster strain (SHR) and normotensive Wistar-Kyoto rats (WKY) . The isometric vasoconstriction of aortic strips was measured using a vessel myograph. After inhibition of sarcoplasmic Ca2+-ATPase by thap sigargin the aortic strips from both SHR and WKY showed a biphasic con tractile response. The maximum increase of aortic tension was in SHR 1 .7 +/- 0.3 mNewton and in WKY 2.1 +/- 0.3 mNewton. The second phase of the contractile response was abolished in the absence of extracellula r calcium or after addition of nifedipine, indicating that the second phase of the contraction may be mediated by the transplasmamembrane ca lcium influx. The initial phase of the contractile response was abolis hed after addition of the intracellular calcium antagonist 8-(diethyla mino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), indicating that the init ial phase of the contractile response was mediated by calcium release from intracellular stores. The results indicate that the inhibition of sarcoplasmic Ca2+-ATPase causes vasoconstriction in aorta from rats.