Inhibition of aldosterone production by pinacidil in vitro

J. Howard Pratt, James K. Rothrock, Jesus Dominguez

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Pinacidil, an antihypertensive agent that opens potassium channels, lowers plasma aldosterone levels in hypertensive patients by an unknown mechanism. In the present study, pinacidil's direct effects on production of aldosterone were assessed using isolated cells from bovine adrenal glomerulosa. Pinacidil was found to inhibit aldosterone production, both basally and during stimulation with either potassium, angiotensin II (Ang II), or adrenocorticotropic hormone (p<0.001), with half maximal inhibition occurring at 10-5 M. As assessed by the exclusion of try pan blue from cells, pinacidil did not inhibit secretion through injurious effects on glomerulosa cells. Also, washing of cells previously exposed to pinacidil restored secretory responsiveness. Pinacidil did not alter cytosolic calcium (Ca2+) concentrations when aequorin was used as a photoluminescent indicator of Ca2+ levels, suggesting that pinacidil acted by a non-Ca2+-mediated mechanism. Consistent with direct inhibition of the late pathway in steroidogenesis was that pinacidil decreased conversion of pregnenolone and corticosterone to aldosterone. Pinacidil did not block binding of Ang II to its receptor, nor did it appear to affect adrenocorticotropic hormone-receptor binding, since stimulation by cyclic AMP, the postreceptor second messenger of adrenocorticotropic hormone, was also inhibited. In summary, pinacidil inhibited directly the adrenal's production of aldosterone. The mechanism whereby the inhibition occurred was unclear.

Original languageEnglish
Pages (from-to)529-534
Number of pages6
JournalHypertension
Volume18
Issue number4
StatePublished - Oct 1991

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Pinacidil
Aldosterone
Angiotensin II
Adrenocorticotropic Hormone
Corticotropin Receptors
In Vitro Techniques
Aequorin
Zona Glomerulosa
Pregnenolone
Potassium Channels
Second Messenger Systems
Corticosterone
Cyclic AMP
Antihypertensive Agents
Potassium

Keywords

  • Aldosterone
  • Pinacidil
  • Potassium

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Pratt, J. H., Rothrock, J. K., & Dominguez, J. (1991). Inhibition of aldosterone production by pinacidil in vitro. Hypertension, 18(4), 529-534.

Inhibition of aldosterone production by pinacidil in vitro. / Pratt, J. Howard; Rothrock, James K.; Dominguez, Jesus.

In: Hypertension, Vol. 18, No. 4, 10.1991, p. 529-534.

Research output: Contribution to journalArticle

Pratt, JH, Rothrock, JK & Dominguez, J 1991, 'Inhibition of aldosterone production by pinacidil in vitro', Hypertension, vol. 18, no. 4, pp. 529-534.
Pratt, J. Howard ; Rothrock, James K. ; Dominguez, Jesus. / Inhibition of aldosterone production by pinacidil in vitro. In: Hypertension. 1991 ; Vol. 18, No. 4. pp. 529-534.
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