Chronic central infusion of aldosterone leads to sympathetic hyperreactivity and hypertension in Dahl S but not Dahl R rats.
Six-week-old Dahl salt-sensitive (S) and -resistant (R) rats received for 2 wk an intracerebroventricular infusion of aldosterone (Aldo) (22.5 ng/h) or vehicle containing artificial cerebrospinal fluid (aCSF) with 0.15 M Na+. At 8 wk, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in conscious rats at rest, in response to air stress, and to an intracerebroventricular injection of the alpha2-adrenoceptor agonists guanabenz or ouabain. Baroreflex control of RSNA and HR was estimated by using intravenous phenylephrine and nitroprusside. In Dahl S but not Dahl R rats, Aldo raised resting MAP by 20-25 mmHg, doubled sympathoexcitatory and pressor responses to air stress and sympathoinhibitory and depressor responses to guanabenz, and impaired baroreflex function. In Dahl S but not Dahl R rats, Aldo significantly increased content of ouabain-like compounds (OLC) in the hypothalamus and attenuated excitatory responses to ouabain. Aldo did not affect water intake, plasma electrolytes, or OLC in plasma and adrenal glands. In another set of three groups of Dahl S rats, Aldo dissolved in aCSF containing 0.16, 0.15, or 0.14 M Na+ was infused intracerebroventricularly for 2 wk. CSF Na+ concentration ([Na+]) showed only a nonsignificant increase, but resting MAP increased from 111 +/- 3 mmHg in rats with Aldo in 0.14 M Na+ to 131 +/- 3 and 147 +/- 3 mmHg with Aldo in 0.15 and 0.16 M Na+, respectively (P < 0.05 for both). These findings indicate that in Dahl S rats, intracerebroventricular infusion of Aldo causes similar central responses as high salt intake, i.e., increases in brain OLC content, sympathetic hyperreactivity, and hypertension. The extent of the increase in blood pressure (BP) by intracerebroventricular Aldo depends on the [Na+] in the vehicle. In Dahl R rats, intracerebroventricular Aldo did not increase brain OLC, sympathetic reactivity, and BP, suggesting that in this rat strain, a decrease in central responsiveness to mineralocorticoids may contribute to its salt-resistant nature.
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Bing S
BS
Huang
Hao
H
Wang
Frans H H
FH
Leenen
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*
D002316:Cardiotonic Agents; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D010042:Ouabain