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(Hypertension. 1998;31:595-602.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Ca²⁺ in the Dense Tubules

A Model of Platelet Ca²⁺ Load

Makoto Horiguchi; Masayuki Kimura; Jonathan Lytton; Joan Skurnick; Frederic Nash; Girgis Awad; Esteban Poch; ; Abraham Aviv

From the Hypertension Research Center and the Department of Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ; and the Renal Division, Departments of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Mass (J.L., E.P.).

Correspondence to Abraham Aviv, MD, Hypertension Research Center, University of Medicine and Dentistry of New Jersey-NJ Medical School, 185 S Orange Ave, MSB F-464, Newark, NJ 07103-2714.

Abstract—In this work, we explored the relationship between the freely exchangeable Ca²⁺ (FECa²⁺) in the dense tubules (DT) and the sarco(endo)plasmic reticulum (SER) Ca²⁺-ATPase (SERCA) in circulating human platelets and examined the relationship between blood pressure (BP) and these platelet parameters. Studying platelets from 32 healthy men, we showed that the maximal reaction velocity (V_max) of the SERCA significantly correlated with FECa²⁺ in the DT and with the protein expressions of SERCA 2 and 3. BP positively correlated with both the V_max of the SERCA (r=.462, P=.010) and the FECa²⁺ sequestered in the DT (r=.492, P=.005). The relationships between these platelet Ca²⁺ parameters and BP were in part confounded by increased levels of serum triglycerides and diminished HDL cholesterol with a higher BP. No correlation was observed between the resting cytosolic Ca²⁺ and BP. Collectively, these findings indicate that (1) an increase in the cellular Ca²⁺ load in platelets is expressed by a higher activity of the SERCA and an increase in the expressions of SERCA 2 and 3 proteins, coupled with an increase in the FECa²⁺ in the DT, and (2) a higher BP is associated with an increase in platelet Ca²⁺ load in human beings, expressed by a rise in the FECa²⁺ in the DT and the upregulation of SERCA activity.

Key Words: hypertension, essential • thapsigargin • lipids • calcium transport • sodium transport

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