Effects of angiotensin type 2 receptor on secretion of the locus coeruleus in stress-induced hypertension rats

Locus coeruleus (LC) has noradrenergic nerve terminals projecting to hypothalamus that modulating cardiovascular activity. To study the dynamic characteristics of norepinephrine (NE) release in hypothalamus followed by electrical stimulation in the locus coeruleus in the stress-induced hypertension (SIH) rats, we established the hypertension model rats by stimulations combining noise and foot-shock stress. After the end of modeling, NE release in the hypothalamus by electrical stimulation in LC was studied and NE signal was recorded by carbon fiber electrode. The peak value, the time to peak and half-life period of NE signal in both group rats were analyzed. Furthermore, to clarify the role of angiotensin II type 2 receptors (AT(2)) in norepinephrine (NE) release and the blood pressure of rat model of stress-induced hypertension, we intraperitoneally administered the AT(2) receptor antagonist PD123319 (AT(2) receptor antagonist, 0.3 mg/kg, i.p.) and intracerebroventricularly injection of CGP42112 (AT(2) receptor agonist, 6 mu g/5 mu l, i.c.v.) to adult male rats. We found the peak value of NE signal in the hypothalamus followed by electrical stimulation in the LC in SIH rats were higher than that in controls (P<0.01). Intraperitoneal injection of PD123319 (AT(2) receptor antagonist) potentiated electrical stimulation in the LC induced NE release in the hypothalamus in SIH rats and elevated blood pressure (P<0.05), whereas intracerebroventricular injection of CGP42112 (AT(2) receptor agonist) inhibited the NE release and reduced the heart rate (P<0.05). These results suggest that combining noise and foot-shock stresses increased the blood pressure and the secretion of NE in the hypothalamus followed by electrical stimulation in the LC in rats. AT2 receptors can inhibit the secretion of NE from the LC to the hypothalamus. The attenuation of presynaptic action of AT(2) receptor may play a role in the pathophysiological mechanism of SIH in rats. (C) 2014 Elsevier Inc. All rights reserved.