Anteroposterior distribution of AT(1) angiotensin receptors in caudal brainstem cardiovascular regulatory centers of the rat.
Angiotensin II acts on Ang II type 1 (AT(1)) receptors in areas of the caudal brainstem involved in cardiovascular regulation. In particular, activation of AT(1) receptors in the rostral ventrolateral medulla (RVLM) has been suggested to contribute to hypertension. However, the characteristics of AT(1) receptors in the RVLM of rat, the species in which the most experimental work has been done, are not well documented. This study evaluated AT(1) 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 (125)I-sarcosine(1), isoleucine(8) angiotensin II to assess the density (B(max)) and dissociation constant (K(D)) of the receptors for the radioligand. The dorsomedial medulla (DMM) displayed a high density of AT(1) 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 AT(1) 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 AT(1) receptors in the caudal brainstem.
Bourassa
Erick A
EA
Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
Sved
Alan F
AF
Speth
Robert C
RC
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002319:Cardiovascular System / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D007457:Iodine Radioisotopes; D007700:Kinetics; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
D007457:Iodine Radioisotopes; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; C014622:angiotensin II, Ile(8)-