Platelet volume responses to cytoplasmic acidification in essential hypertension.
Using a Coulter-based cell sizing method, we have previously demonstrated that, in response to cytoplasmic acidification by 140 mmol/l sodium propionate, both the mean initial rate of amiloride-sensitive platelet volume swelling and the net volume change achieved at steady-state are greater in essential hypertensives than in normotensives. In the present study, we extend this observation by showing that, in response to graded propionate exposure (56-140 mmol/l), steady-state amiloride-sensitive volume responsiveness (as percentage increase over baseline) increases linearly, and the mean slope of the line relating amiloride-sensitive volume change and propionate concentration is increased in hypertensives (0.40 +/- 0.02 versus 0.32 +/- 0.02% per mmol/l propionate, P less than 0.003). In 56 mmol/l propionate, average amiloride-sensitive platelet swelling is significantly less in hypertensives than in normotensives (7.6 +/- 0.8 versus 11.1 +/- 0.9%, P less than 0.05), but in 140 mmol/l propionate, swelling is significantly increased in hypertensives (40.8 +/- 1.7 versus 36.2 +/- 1.5%, P less than 0.05). Since platelet intracellular calcium concentration is elevated in some hypertensives and Ca2+ is known to stimulate Na(+)-H+ antiport, the transport system that is the primary determinant of amiloride-sensitive cell swelling during propionate incubation, we studied the effects of the Ca2+ ionophore, ionomycin, on volume regulation. In both normotensives and hypertensives, ionomycin (2 x 10(-10 to 2 x 10(-7) mol/l) causes dose-related increases in amiloride-sensitive platelet swelling during graded propionate exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Weder
A B
AB
Department of Internal Medicine, University of Michigan Hospitals, Ann Abor.
Schmouder
R L
RL
Torretti
B A
BA
D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000097:blood*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D011422:Propionates / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D011422:Propionates; D017923:Sodium-Hydrogen Exchangers; D015759:Ionomycin; D000584:Amiloride; C514135:sodium propionate; C029658:propionic acid; D002118:Calcium