Depressor systems contribute to hypertension induced by glucocorticoid excess in dogs.
OBJECTIVE
The aim of this study was to investigate the role of depressor systems in glucocorticoid-induced hypertension.


METHODS
The serial changes in cardiorenal hemodynamics, urinary excretions of kallikrein and prostaglandins (PGE2 and the prostacyclin derivative 6-keto-PGF1 alpha) before, and during the administration of both low and high doses of dexamethasone (9 alpha-fluoro-16 alpha-methylprednisolone) and after the cessation of dexamethasone were examined in conscious trained dogs. In addition, pressor responses to prostaglandin, bradykinin, bradykinin antagonist and indomethacin were studied during the administration of dexamethasone.


RESULTS
High-dose dexamethasone induced a significant elevation in mean arterial pressure (MAP) that was accompanied by a significant reduction in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. In contrast, low-dose dexamethasone treatment had no significant effect upon MAP but induced a transient elevation in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. Furthermore, additional oral administration of indomethacin produced a significant elevation in MAP in dogs treated with low-dose dexamethasone; but did not affect the hemodynamics of animals with high-dose dexamethasone. Whilst i.v. administration of either bradykinin or prostacyclin induced a significant reduction in MAP in high-dose but not low-dose dexamethasone-treated dogs, administration of a competitive bradykinin antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-bradykinin induced a significant elevation in MAP in low-dose but not high-dose dexamethasone-treated dogs.


CONCLUSIONS
Depressor systems play an important role in regulation of blood pressure in glucocorticoid-treated dogs.
Nakamoto
H
H
Department of Internal Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Kageyama
Y
Y
Murakami
M
M
Ohishi
A
A
Naitoh
M
M
Ichihara
A
A
Saruta
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003907:Dexamethasone / Q000008:administration & dosage; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005938:Glucocorticoids / Q000008:administration & dosage*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007213:Indomethacin / Q000008:administration & dosage; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D013997:Time Factors
D005938:Glucocorticoids; D011453:Prostaglandins; C053748:B 4162; D003907:Dexamethasone; D001920:Bradykinin; D007213:Indomethacin