Angiotensin 1-7 has a biphasic effect on fluid absorption in the proximal straight tubule.
The effect of angiotensin 1-7 (Ang 1-7) on the proximal tubule has not been well studied. It was hypothesized that Ang 1-7 has a biphasic effect on fluid absorption in the isolated rat proximal straight tubule. Proximal straight tubules were perfused at a rate of 5.81 +/- 0.44 nL/mm per minute and absorbed fluid at 0.98 +/- 0.10 nL/mm per minute. Bicarbonate absorption was 80.1 +/- 11.6 pmol/mm per minute. When 10(-12) M Ang 1-7 was added to the bath, fluid absorption increased to 1.47 +/- 0.10 nL/mm per minute (P < 0.013) and bicarbonate increased to 115.0 +/- 12.8 pmol/mm per minute (P < 0.004). Ang 1-7 had no effect on either the maximum rate of bicarbonate absorption (P > 0.90) or bicarbonate permeability (P > 0.60). Next, 10(-8) M Ang 1-7 was used. During the control period, fluid absorption was 0.90 +/- 0.09 nL/mm per minute. When 10(-8) M Ang 1-7 was added, fluid absorption decreased to 0.62 +/- 0.04 nL/mm per minute (P < 0.05). DuP 753, an AT1 receptor antagonist, blocked both effects induced by Ang 1-7, whereas PD 123319, an AT2 receptor antagonist, did not block the stimulatory effect. From these data, it was concluded that Ang 1-7 binds AT1 receptors and has a biphasic effect on fluid absorption, and at physiologic levels, the heptapeptide induces the stimulation of bicarbonate absorption.
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202.
N H
NH
Garcia
J L
JL
Garvin
D000327:Adsorption / Q000187:drug effects; D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D019808:Losartan; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D010539:Permeability / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001639:Bicarbonates; D001713:Biphenyl Compounds; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan