Control of vascular changes by renin-angiotensin-aldosterone system in salt-sensitive hypertension.
The purpose of this study was to investigate the role of the renin-angiotensin-aldosterone system in hypertension development and cardiovascular structural changes in a salt-sensitive hypertensive model induced by capsaicin (CAP). Newborn male Wistar rats were injected with either capsaicin or vehicle. After weaning at 3 weeks, these rats were divided into the following six treatment groups: capsaicin plus high-salt diet (CAP+HS), control plus high-salt diet (CON+HS), control plus normal salt diet (CON+NS), capsaicin plus high-salt diet and telmisartan (CAP+HS+T, 10 mg/kg/day), capsaicin plus high-salt diet and perindopril (CAP+HS+P, 2 mg/kg/day), and capsaicin plus high-salt diet and spironolactone (CAP+HS+S, 80 mg/kg/day). Treatment with different salt diets and drugs was initiated at 3 weeks of age and lasted 18 weeks. We found that beginning at the second week after the initiation of the treatment, blood pressure became significantly higher in CAP+HS than in other groups, accompanied by the development of cardiac hypertrophy. Treatment with telmisartan, perindopril or spironolactone prevented the development of hypertension in the CAP+HS group. Cardiac hypertrophy was prevented in the perindopril treatment group. The medial thickness, media-to-lumen ratio and cross-sectional area of the thoracic, renal and mesenteric arteries were significantly increased in CAP+HS than in other groups. Lumen diameter was similar in all the vessels among all the groups. Treatment with telmisartan, perindopril or spironolactone prevented the development of vascular remodeling, as found in the CAP+HS group. Beginning at 8 weeks after the initiation of the salt diet treatment (11 weeks of age), blood pressure also became higher in CON+HS than in CON+NS, but lower than CAP+HS. Structural changes of vessels were also present in CON+HS, but the degree of change was less when compared with CAP+HS. We conclude that neonatal treatment with capsaicin plus a high-salt diet, and a high-salt diet alone both induced hypertension development in normal Wistar rats, which are associated with cardiovascular remodeling. The renin-angiotensin-aldosterone system is involved in this salt-sensitive model because treatment that interfered with this system also prevented the development of hypertension and vascular remodeling.
Zeng
Zhao-Hua
ZH
Smooth Muscle Research Program and Department of Anesthesia, McMaster University, Department of Anesthesiology (HSC-2u3), 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Luo
Bi-Hui
BH
Gao
Yu-Jing
YJ
Su
Cheng-Jian
CJ
He
Chao-Chu
CC
Yi
Jia-Ji
JJ
Li
Nina
N
Lee
Robert M K W
RM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology; D001158:Arteries / Q000473:pathology / Q000503:physiopathology; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D002211:Capsaicin; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D020913:Perindopril / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012982:Sodium, Dietary / Q000009:adverse effects*; D013148:Spironolactone / Q000494:pharmacology; D000077333:Telmisartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D000451:Mineralocorticoid Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D012982:Sodium, Dietary; D013148:Spironolactone; D002211:Capsaicin; D000077333:Telmisartan; D020913:Perindopril