The hyperglycemia induced by angiotensin II in rats is mediated by AT1 receptors.
We have shown that the renin-angiotensin system (RAS) is involved in glucose homeostasis during acute hemorrhage. Since almost all of the physiological actions described for angiotensin II were mediated by AT1 receptors, the present experiments were designed to determine the participation of AT1 receptors in the hyperglycemic action of angiotensin II in freely moving rats. The animals were divided into two experimental groups: 1) animals submitted to intravenous administration of angiotensin II (0.96 nmol/100 g body weight) which caused a rapid increase in plasma glucose reaching the highest values at 5 min after the injection (33% of the initial values, P < 0.01), and 2) animals submitted to intravenous administration of DuP-753 (losartan), a non-peptide antagonist of angiotensin II with AT1-receptor type specificity (1.63 mumol/100 g body weight as a bolus, i.v., plus a 30-min infusion of 0.018 mumol 100 g body weight-1 min-1 before the injection of angiotensin II), which completely blocked the hyperglycemic response to angiotensin II (P < 0.01). This inhibitory effect on glycemia was already demonstrable 5 min (8.9 +/- 0.28 mM, angiotensin II, N = 9 vs 6.4 +/- 0.22 mM, losartan plus angiotensin II, N = 11) after angiotensin II injection and persisted throughout the 30-min experiment. Controls were treated with the same volume of saline solution (0.15 M NaCl). These data demonstrate that the angiotensin II receptors involved in the direct and indirect hyperglycemic actions of angiotensin II are mainly of the AT1-type.
Machado
L J
LJ
Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
Marubayashi
U
U
Reis
A M
AM
Coimbra
C C
CC
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000009:adverse effects*; D000809:Angiotensins / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D006943:Hyperglycemia / Q000139:chemically induced*; D019808:Losartan / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects*
D000809:Angiotensins; D000959:Antihypertensive Agents; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000803:Angiotensin I; D019808:Losartan