Summary The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.

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Thunhorst RL, Grobe CL, Beltz TG, Johnson AK. Effects of ␤-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats. Am J Physiol Regul Integr Comp Physiol 300: R1001-R1008, 2011. First published February 9, 2011 doi:10.1152/ajpregu.00737.2010.-These experiments examined water-drinking and arterial blood pressure responses to ␤-adrenergic receptor activation in young (4 mo), "middle-aged" adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate ␤1-and ␤2-adrenergic receptors, salbutamol to selectively activate ␤2-adrenergic receptors, and the combination of isoproterenol and the ␤2-adrenergic receptor antagonist ICI 118,551 to stimulate only ␤1-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The ␤2-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in ␤-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after ␤-adrenergic receptor stimulation. aging; water intake; heart rate; renin activity; hematocrit; aldosterone ISOPROTERENOL IS A MIXED ␤ 1 , ␤ 2 -adrenergic receptor agonist that causes hypotension (6,16,21,31,35), tachycardia (6, 9, 21), renin secretion (21, 26), and water drinking (16, 17, 21, 31) upon administration. The ␤ 1 and ␤ 2 receptor subtypes contribute differently to the effects of isoproterenol. Stimulation of myocardial ␤ 1 -adrenergic receptors increases heart rate (HR) (21, 35) and strength of contraction (7,22). Activation of other ␤ 1 -adrenergic receptors located on the juxtaglomerular apparatus of the kidney releases renin (21, 26). Stimulation of vascular ␤ 2 -adrenergic receptors causes vasodilation and reductions in arterial pressure, which reflexively increase HR and renin secretion through baroreceptor mechanisms (21, 26). The water drinking response is a result of isoproterenol-induced hypotension and renin secretion (21,26,31).Several studies have used isoproterenol to examine agerelate...

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