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Glucocorticoids and atrial natriuretic factor receptors on vascular smooth muscle
K Yasunari1, M Kohno, K Murakawa
1First Department of Internal Medicine, Osaka City University Medical School, Japan.
Abstract:
The effect of glucocorticoids on the atrial natriuretic factor (ANF)-mediated formation of cyclic guanosine monophosphate (cGMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from the renal arteries of 14-week-old Wistar rats by the explant method. Micromolar concentrations of dexamethasone, given as pretreatment for 48 hours, suppressed the ANF-mediated response. The dexamethasone-induced suppression was detectable at 6 hours and reached a maximum 24 hours after administration in a dose-dependent manner. Inhibitors of protein synthesis blocked this effect of the glucocorticoid. The basal activity of guanylate cyclase in the dexamethasone-treated cells was lower than in the control cells. Other steroids having glucocorticoid action mimicked this suppression of the ANF-mediated response. This suppression was blocked by a glucocorticoid receptor antagonist. The results suggest that glucocorticoids suppress ANF-mediated cGMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis. Suppression of the ANF-mediated response may play a role in glucocorticoid-induced hypertension.
Insights
Glucocorticoids suppress atrial natriuretic factor (ANF)-mediated cyclic guanosine monophosphate (cGMP) formation in vascular smooth muscle cells (VSMC). This effect, mediated by glucocorticoid receptors and protein synthesis, may contribute to glucocorticoid-induced hypertension.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Molecular Pharmacology
Background:
- Atrial natriuretic factor (ANF) plays a crucial role in regulating blood pressure and fluid balance.
- Vascular smooth muscle cells (VSMC) are key effectors in cardiovascular regulation.
- Glucocorticoids are known to influence cardiovascular function and can induce hypertension.
Purpose of the Study:
- To investigate the effect of glucocorticoids on ANF-mediated cyclic guanosine monophosphate (cGMP) formation in VSMC.
- To elucidate the cellular mechanisms underlying glucocorticoid action on ANF signaling.
- To explore the potential link between glucocorticoid-induced suppression of ANF signaling and hypertension.
Main Methods:
- Primary cultured VSMC were isolated from Wistar rat renal arteries using the explant method.
- Cells were pretreated with dexamethasone (a glucocorticoid) for varying durations and concentrations.
- ANF-mediated cGMP formation, guanylate cyclase activity, and the effects of protein synthesis inhibitors and receptor antagonists were assessed.
Main Results:
- Dexamethasone pretreatment suppressed ANF-mediated cGMP formation in a dose- and time-dependent manner.
- The suppressive effect was blocked by inhibitors of protein synthesis, indicating a requirement for new protein synthesis.
- Basal guanylate cyclase activity was reduced in dexamethasone-treated cells, and the effect was mimicked by other glucocorticoids and blocked by a glucocorticoid receptor antagonist.
Conclusions:
- Glucocorticoids suppress ANF-mediated cGMP formation in VSMC via glucocorticoid type II receptors and induction of protein synthesis.
- This suppression of ANF signaling may be a contributing factor to the development of glucocorticoid-induced hypertension.
- Understanding this mechanism provides insights into the cardiovascular effects of glucocorticoids.