The glucocorticoid receptor is required for experimental adrenocorticotrophic hormone-induced hypertension in mice.
1. In the present study, we have (i) measured basal blood pressure by telemetry in wild-type (WT) and glucocorticoid receptor knockout (GRKO) mice; (ii) investigated whether or not adrenocorticotrophic hormone (ACTH) can induce hypertension in GRKO mice; and (iii) investigated the effect of mineralocortocoid receptor blockade on the cardiovascular physiology of GRKO mice. 2. Male WT and GRKO mice were treated with ACTH (2mg/kg per day s.c.) or spironolactone (100mg/kg per day s.c.) for 1-2weeks. Blood pressure (BP) was measured using a radiotelemetry system. Urinary Na:K, blood glucose concentrations and haematocrit were also measured during the treatment period. 3. Baseline systolic blood pressure (SBP) was higher in GRKO mice (126±4 mmHg, mean±SEM, n=11) than WT mice (114±2mmHg, n=10; P<0.05). There was no significant difference in baseline haematocrit, blood glucose and urine Na:K ratio in WT and GRKO mice. ACTH raised SBP in WT (135±8mmHg, n=8; P<0.05), but not in GRKO mice (113±9mmHg, n=6). Spironolactone treatment did not alter SBP. 4. Basal SBP was higher in GRKO than WT mice; ACTH raised blood pressure in WT, but not GRKO mice; and spironolactone did not alter BP in GRKO or WT mice. These data, together with a previous study showing both ACTH and corticosterone are increased in GRKO mice, show that the GR is required for the development of ACTH-induced hypertension in mice. Increased endogenous ACTH levels in this model might contribute to the increased basal SBP in GRKO mice, possibly through residual fragments of GR. Mineralocorticoid receptors do not appear to play a critical role in maintaining BP in glucocorticoid receptor deficient mice.
Zhang
Yi
Y
Cardiovascular Research, the Canberra Hospital, Garran, ACT,Australia. yi.zhang@act.gov.au
Schyvens
Christopher G
CG
Cole
Timothy J
TJ
McKenzie
Katja U S
KU
Vickers
Janine J
JJ
Whitworth
Judith A
JA
D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists; D009929:Organ Size / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology*; D013148:Spironolactone / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D013148:Spironolactone; D000324:Adrenocorticotropic Hormone