11beta-hydroxysteroid dehydrogenase in human vascular cells.

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Molecular Biology

Background:

• Aldosterone selectivity in target tissues is primarily mediated by 11beta-hydroxysteroid dehydrogenase (11betaHSD).
• 11betaHSD type 2 (11betaHSD2) is crucial for mineralocorticoid receptor (MR) ligand specificity.
• Diminished vascular 11betaHSD activity has been observed in hypertensive rats, but the underlying mechanism remains unclear.

Purpose of the Study:

• To investigate the role of vascular 11betaHSD activity in regulating blood pressure.
• To elucidate the mechanism linking impaired 11betaHSD activity to elevated blood pressure in vascular smooth muscle cells.

Main Methods:

• Enzyme activity assays in human coronary artery smooth muscle cells.
• Inhibition of 11betaHSD2 using antisense DNA targeting 11betaHSD2 mRNA.
• Measurement of angiotensin II (Ang II) binding.
• Use of a selective aldosterone receptor antagonist.

Main Results:

• Cortisol increases vascular tone by up-regulating pressor hormone receptors like Ang II.
• Inhibition of 11betaHSD2 activity significantly enhanced cortisol-induced Ang II binding.
• This enhancement was partially reversed by an aldosterone receptor antagonist, suggesting cortisol acts as a mineralocorticoid.

Conclusions:

• Impaired vascular 11betaHSD activity contributes to increased vascular tone and elevated blood pressure.
• Cortisol can act as a mineralocorticoid in the vasculature when 11betaHSD activity is deficient.
• Vascular 11betaHSD activity influences blood pressure independent of renal sodium retention mechanisms.