Use of positron emission tomography to study AT1 receptor regulation in vivo.
Increased sodium intake and enhanced sodium sensitivity are implicated in the pathogenesis of hypertension and in the control of a major regulator of BP, the type 1 angiotensin receptor (AT(1) receptor). An in vivo technique to study changes of renal AT(1) receptors by dietary sodium was developed that uses positron emission tomography (PET). PET revealed that renal cortical AT(1) receptor binding was increased in sodium-loaded compared with sodium-deprived dogs, which correlated with ex vivo estimations of AT(1) receptor numbers. Plasma renin activity, angiotensin II, and aldosterone were inversely related to changes in AT(1) receptor binding. These results demonstrate, for the first time in vivo, that the renal AT(1) receptor is inversely related to the activity of the renin angiotensin system, which may provide a compensatory mechanism to prevent inappropriate fluctuations in arterial BP. The ability to measure AT(1) receptor binding in vivo has potential significance for clinical studies of AT(1) receptors, because PET is a noninvasive imaging technique that is readily applicable in humans.
Szabo
Zsolt
Z
Division of Nuclear Medicine, The Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland.
Speth
Robert C
RC
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, and Department of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, Oregon.
Brown
P Randy
PR
Division of Comparative Medicine, The Johns Hopkins University, Baltimore, Maryland.
Kerenyi
Levente
L
Division of Nuclear Medicine, The Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland.
Kao
Pan Fu
PF
Chang Gung Memorial Hospital, Department of Nuclear Medicine, Taipei, Taiwan.
Mathews
William B
WB
Division of Nuclear Medicine, The Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland.
Ravert
Hayden T
HT
Division of Nuclear Medicine, The Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland.
Hilton
John
J
Division of Nuclear Medicine, The Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland.
Rauseo
Paige
P
Division of Nuclear Medicine, The Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland.
Dannals
Robert F
RF
Division of Nuclear Medicine, The Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland.
Zheng
Wei
W
Division of Nephrology and Hypertension, Georgetown University, Washington, DC.
Lee
Sunghou
S
Division of Nephrology and Hypertension, Georgetown University, Washington, DC.
Sandberg
Kathryn
K
Division of Nephrology and Hypertension, Georgetown University, Washington, DC.
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004285:Dogs; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012083:Renin / Q000097:blood; D012982:Sodium, Dietary / Q000494:pharmacology; D014055:Tomography, Emission-Computed
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000804:Angiotensin II; C099071:L 159884; D000450:Aldosterone; D012083:Renin