Anteroposterior distribution of AT1 angiotensin receptors in caudal brainstem cardiovascular regulatory centers of the rat

Angiotensin II acts on Ang II type 1 (AT1) receptors in areas of the caudal brainstem involved in cardiovascular regulation. In particular, activation of AT1 receptors in the rostral ventrolateral medulla (RVLM) has been suggested to contribute to hypertension. However, the characteristics of AT1 receptors in the RVLM of rat, the species in which the most experimental work has been done, are not well documented. This study evaluated AT1 receptor binding along a 2.7-mm length of rat medulla, which included the full extent of the RVLM and the caudal ventrolateral medulla (CVLM). Sections of medulla from female rats cut on a cryostat were incubated with five concentrations of 125I-sarcosine1, isoleucine8 angiotensin II to assess the density (Bmax) and dissociation constant (KD) of the receptors for the radioligand. The dorsomedial medulla (DMM) displayed a high density of AT1 binding (1207 ± 100 fmol/g), which peaked at 0.4 mm rostral to the calamus scriptorius (approximately 14 mm caudal to Bregma). The RVLM and CVLM displayed significantly lower (p < 0.01) densities of AT1 binding, 278 ± 38 and 379 ± 64 fmol/g, respectively. However, the dissociation constants were significantly lower (i.e., higher affinity) in RVLM and CVLM (164 ± 38 and 178 ± 27 pM, respectively,) than in DMM (328 ± 12 pM, p < 0.01 and p < 0.05, respectively). These results provide an anatomical and pharmacological framework for future studies on the role in cardiovascular regulation of AT1 receptors in the caudal brainstem.