Regulation of jejunal sodium and water absorption by angiotensin subtype receptors.
The purpose of this study was to determine the precise role of angiotensin subtype-1 (AT1) and -2 (AT2) receptors and the mechanisms by which they act to alter fluid transport in the rat jejunum. In rats on normal sodium intake, ANG II at low dose stimulated net jejunal fluid absorption, whereas at a high dose the peptide inhibited absorption. Low-dose ANG II-stimulated fluid absorption was blocked completely by the specific AT2 receptor antagonist PD-123319 (PD) but was unchanged by the AT1 receptor antagonist losartan (Los). The AT2 receptor agonist CGP-42112A, caused an inversely dose-dependent increase in fluid absorption, which also was totally prevented by PD but was unaltered by Los. Conversely, high-dose ANG II inhibition of absorption was blocked by Los but not by PD. In animals receiving normal sodium intake, neither Los nor PD alone altered fluid absorption. In sodium-restricted animals, however, Los alone increased absorption and PD alone inhibited absorption. In rats on normal sodium intake, low-dose ANG II increased jejunal interstitial and luminal (loop) fluid concentrations of cGMP. These increases in cGMP were blocked with PD but not with Los. 8-Bromoguanosine-3',5'-cyclic monophosphate administered via the mesenteric artery or the submucosal interstitial space markedly increased absorption, but it inhibited absorption when administered into the loop. High-dose ANG II decreased jejunal interstitial and loop fluid cAMP and increased PGE2. The increase in PGE2 was blocked by Los but not by PD. The data demonstrate that ANG II mediates jejunal sodium and water absorption by an action at the AT2 receptor involving cGMP formation. The data also show that ANG II inhibits absorption via the AT1 receptor by a mechanism that is both negatively coupled to cAMP and increases jejunal PGE2 production.
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
X H
XH
Jin
Z Q
ZQ
Wang
H M
HM
Siragy
R L
RL
Guerrant
R M
RM
Carey
D058668:Adrenergic alpha-1 Receptor Antagonists; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006145:Guanethidine / Q000494:pharmacology; D006706:Homeostasis; D007093:Imidazoles / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000819:agonists / Q000502:physiology*; D013997:Time Factors; D014867:Water
D058668:Adrenergic alpha-1 Receptor Antagonists; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014867:Water; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D006152:Cyclic GMP; D019808:Losartan; D015232:Dinoprostone; D011224:Prazosin; D006145:Guanethidine