Vasopressin V1a receptor antagonism does not reverse adrenocorticotrophin-induced hypertension in the rat.
1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrophin (ACTH)-induced hypertension in Sprague-Dawley rats using the non-peptide AVP V1a receptor antagonist OPC 21268. 2. In an acute study, six rats were pretreated with ACTH for 11 days and direct arterial blood pressure (4 h), plasma osmolality and electrolyte concentrations were measured after OPC 21268 gavage. In a chronic study, 40 rats were randomly divided into four groups: (i) sham injection + sham gavage; (ii) ACTH + sham gavage; (iii) sham injection + OPC 21268; or (iv) ACTH + OPC-21268 for 16 days. Systolic blood pressure (SBP), water intake, urine volume (UV), urine osmolality and electrolytes, food intake, bodyweight and plasma osmolality and electrolyte concentrations were measured. 3. In the acute study, direct mean arterial blood pressure did not change with OPC 21268 (122+/-2 and 120+/-3 mmHg at 0 and 240 min, respectively). 4. In the chronic study, OPC 21268 did not affect ACTH-induced rises in blood pressure (from 125+/-2 (control) to 145+/-5 mmHg (group 4) compared with 122+/-3 (control) to 149+/-5 mmHg (group2)). Water intake and UV increased (from 29+/-2 to 83+/-6 mL/day; and from 5+/-1 to 36+/-5 mL/day, respectively) and the change in bodyweight decreased from 0+/-2 to -107+/-7 g. 5. These results suggest that AVP (at the V1a receptor) does not play a significant role in the maintenance of ACTH-induced hypertension.
Fraser
T B
TB
Department of Medicine, St George Hospital, The University of New South Wales, Sydney, Australia.
Turner
S W
SW
Wen
C
C
Li
M
M
Burrell
L M
LM
Whitworth
J A
JA
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006400:Hematocrit; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D009994:Osmolar Concentration; D010880:Piperidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014563:Urodynamics / Q000187:drug effects
D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; C068644:OPC 21268; D000324:Adrenocorticotropic Hormone