Angiotensin II AT1 receptor blockade prolongs the lifespan of spontaneously hypertensive rats and reduces stress-induced release of catecholamines, glucocorticoids, and vasopressin.
A 2-week pretreatment with an Angiotensin II AT(1) antagonist prevented the adrenomedullary and hormonal response to isolation stress. We studied the effect of life-long treatment with the AT(1) receptor antagonist candesartan, 10 mg/kg/day, or vehicle administered orally in the drinking water from 8 weeks of age on the response to stress of stress-sensitive spontaneously hypertensive rats (SHRs) and their normotensive controls, the Wistar Kyoto (WKY). Rats were submitted to 24-h isolation stress at different times during the treatment. Treatment with candesartan extended the lifespan of SHRs. AT(1) receptor blockade retained its capacity to blunt the response to isolation stress over a long period of treatment. The AT(1) antagonist inhibited epinephrine release in SHR but not in WKY rats during the first 3 months, corticosterone release in SHR and WKY rats during 10 months, and vasopressin release in SHR rats during 18 months of treatment when rats were submitted to isolation stress. There were no changes in vasopressin release in WKY rats during stress or after AT(1) receptor blockade. We conclude that the blockade of the stress response by the AT(1) receptor antagonist is long lasting and differs between stress-prone SHR and WKY rats and that the specific components of the stress response (sympathoadrenal activity, hypothalamic-pituitary-adrenal axis activation, and vasopressin release) react differently to AT(1) receptor blockade. The long-term protective effects of AT(1) receptor blockade can be important in animals vulnerable to stress and, in conjunction with the normalization of blood pressure, can prolong lifespan through end-organ protection.
Baiardi
Gustavo
G
Section on Pharmacology, DIRP, NIMH, NIH, DHHS, 10 Center Drive, Bldg. 10, Room 2D-57, Bethesda, MD 20892, USA. baiardig@intra.nimh.nih.gov
Bregonzio
Claudia
C
Jezova
Miroslava
M
Armando
Ines
I
Saavedra
Juan M
JM
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D002395:Catecholamines; D005938:Glucocorticoids; D011945:Receptors, Angiotensin; D014667:Vasopressins; D000804:Angiotensin II