Functional expression of angiotensin II receptors in type-I cells of the rat carotid body

Abstract

Angiotensin II increases afferent discharge from the carotid body in vitro. We hypothesized that angiotensin II receptors (AT receptors) are expressed functionally in the type-I cell of the carotid body. Cytosolic free [Ca 2+] ([Ca 2+] i) in type-I cells freshly dissociated from rat carotid bodies was measured spectrofluorimetrically. Angiotensin II (10-100 nM) concentration-dependently increased [Ca 2+] i in type-I cells. The [Ca 2+] i response was blocked by pretreatment with losartan (1 μM), an AT 1 receptor antagonist, but not by blockade of AT 2 receptors with PD-123319 (1 μM). Moreover, the gene expression of AT 1 receptors was assessed by the reverse transcriptase polymerase chain reaction and gene transcripts of both AT 1a and AT 1b receptors were detected in the carotid body. In addition, immunohistochemical study revealed that AT 1 immunoreactivity was localized in lobules of type-I cells in the carotid body. Taken together, these results suggest that type-I cells in the rat carotid body express functional angiotensin II receptors. The binding of angiotensin II to the AT 1 receptors increases [Ca 2+] i, a key step of the intracellular signalling cascade following the activation of the receptors. It is concluded that angiotensin II modulates carotid body chemoreceptor function directly via AT 1 receptors in the type-I cell.