Effects of chronic central administration of losartan on the cardiovascular and hormonal responses to hemorrhage in conscious rats.

Our objective was to assess the effects of chronic central angiotensin II (Ang II) blockade on the basal regulation of blood pressure, heart rate (HR), arginine vasopressin (AVP), renin, epinephrine (EPI), norepinephrine (NE) and on cardiovascular and hormonal responses to hemorrhage in conscious rats. Losartan (4 micrograms/h), or artificial cerebrospinal fluid (aCSF), was chronically infused into a lateral ventricle by using an osmotic minipump for 6 days at a rate of 1 microliter/h. Compared with aCSF controls, chronic losartan treatment significantly decreased the basal level of blood pressure (from 117 +/- 2.3 to 106 +/- 2.2 mmHg, P < 0.01) and increased the HR (from 357 +/- 3.7 to 410 +/- 6.6 beats/min, P < 0.01). Plasma renin concentration increased 3-fold (from 6.1 +/- 0.6 to 19.2 +/- 1.6 ng.ml(-1).h(-1), P < 0.01). Basal levels of AVP, EPI and NE were not different between two groups. Blood pressure immediately after hemorrhage and its compensatory recovery following hemorrhage was not different in both groups. Immediately after hemorrhage, however, in the losartan-treated rats, the HR was distinctly lower than that of aCSF controls, even at 10 min after hemorrhage. Hemorrhage produced a significant increase in the plasma concentrations of AVP, renin, EPI and NE. Chronic losartan treatment markedly augmented the AVP, renin and EPI responses to hemorrhage. These results strongly suggest that Ang II acting through AT1 receptors in the brain plays a significant physiological role in the regulation of basal blood pressure, HR and renin release. In addition, centrally acting Ang II may be one of the important mediators for cardiovascular regulations and hormone releases in response to hemorrhage.