A critical role for vascular smooth muscle in acute glucocorticoid-induced hypertension.
Although glucocorticoid (GC)-induced hypertension has commonly been attributed to promiscuous activation of the mineralocorticoid receptor by cortisol, thereby promoting excess reabsorption of sodium and water, numerous lines of evidence indicate that this is not the only or perhaps even the primary mechanism. GC induce a number of effects on vascular smooth muscle (VSM) in vitro that may be pertinent to hypertension, but their contribution in vivo is unknown. To address this question, a mouse model with a tissue-specific knockout (KO) of the GC receptor in the VSM was created and characterized. Similar to control mice, KO mice exhibited normal baseline BP and, interestingly, showed normal circadian variation in BP. When dexamethasone was administered, however, the acute hypertensive response was markedly attenuated in KO mice, and there was a trend toward a decreased chronic hypertensive response. These data suggest that the GC receptor in VSM plays a critical role in the acute hypertensive response to GC in vivo.
Goodwin
Julie E
JE
Section of Nephrology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8029, USA.
Zhang
Junhui
J
Geller
David S
DS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009318:Natriuresis / Q000187:drug effects; D010641:Phenotype; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D005938:Glucocorticoids; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011965:Receptors, Glucocorticoid; C051615:transgelin; D003907:Dexamethasone; C045073:Cre recombinase; D019426:Integrases