Tissue-specific response to interstitial angiotensin II in humans.
Angiotensin II is synthesized locally in various tissues; however, the role of interstitial angiotensin II in the regulation of regional metabolism and tissue perfusion is not clear. We characterized the effect of interstially applied angiotensin II in skeletal muscle and subcutaneous adipose tissue of young, normal-weight, healthy subjects by using the microdialysis technique. Furthermore, we tested the hypothesis that the effect of interstitial angiotensin II is modulated by nitric oxide. Tissues were perfused with 0.01, 0.1, and 1 micro mol/L angiotensin II in the presence of the L- or D-isomer of N(G)-nitro-arginine-methyl ester (L- or D-NAME), the effective and noneffective isomer, respectively, for blocking nitric oxide synthase. Dialysate ethanol, glycerol, glucose, lactate, and pyruvate concentrations were measured to assess changes in blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. Baseline blood flow and dialysate concentrations of the metabolites were similar with L- and D-NAME in both tissues. Blood flow and dialysate glucose and lactate did not change significantly in both tissues during perfusion with angiotensin II. Dialysate glycerol dose-dependently increased in adipose tissue (P<0.0438) but decreased in muscle (P<0.007). In muscle, dialysate pyruvate increased (P<0.0002), whereas lactate/pyruvate ratio decreased (P<0.001), both dose-dependently. All effects were similar with L- and D-NAME and could be reversed by nitroprusside. We conclude that in contrast to the profound hemodynamic effect of intravascular angiotensin II, interstitial angiotensin II has a minimal acute effect on blood flow in both tissues. However, interstitial angiotensin II modulates lipid and carbohydrate metabolism in a tissue specific fashion. Thus, the physiology of interstitial angiotensin II cannot be predicted from intravascular studies.
Boschmann
Michael
M
German Institute of Human Nutrition, Department of Biochemistry and Physiology of Nutrition, Potsdam, Germany. boschman@mail.dife.de
Jordan
Jens
J
Adams
Frauke
F
Christensen
Niels-Juel
NJ
Tank
Jens
J
Franke
Gabriele
G
Stoffels
Mandy
M
Sharma
Arya M
AM
Luft
Friedrich C
FC
Klaus
Susanne
S
D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism; D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000032:analysis; D008066:Lipolysis; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000032:analysis; D009928:Organ Specificity; D010477:Perfusion; D019289:Pyruvic Acid / Q000032:analysis; D012039:Regional Blood Flow / Q000187:drug effects
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D019344:Lactic Acid; D019289:Pyruvic Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine