Angiotensin II overflow from canine skeletal muscle in vivo: importance of plasma angiotensin I.
The overflows (i.e., veno-arterial concentration differences multiplied by plasma flow) of angiotensin-(1-10) decapeptide (ANG I) and angiotensin-(1-8) octapeptide (ANG II) from blood-perfused canine gracilis muscle in situ were studied. Special precautions were taken to minimized ex vivo generation and/or degradation of angiotensins in the sampled blood. ANG I was found to be generated in the catheter system supplying the gracilis muscle with arterial blood, but plasma renin activity and ANG II levels were uninfluenced by the catheter system. A positive venoarterial concentration difference over the muscle itself was found for ANG II but not for ANG I under basal conditions. Isoprenaline elicited vasodilatation, reduced ANG I overflow, and tended to increase ANG II overflow, whereas beta-adrenoceptor blockade by propranolol had no effect on these variables. In conclusion, we found no evidence for a local de novo synthesis of ANG II from the gracilis muscle vasculature in vivo. The net overflow of ANG II was most likely caused by local conversion in the tissue of ANG I artifactually generated in the arterial catheter system. beta-Adrenoceptor stimulation enhanced the local conversion of ANG I to ANG II, probably by exposing a greater endothelial surface containing angiotensin-converting enzyme activity.
Schwieler
J H
JH
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Nussberger
J
J
Kahan
T
T
Hjemdahl
P
P
D000803:Angiotensin I / Q000097:blood*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009132:Muscles / Q000098:blood supply / Q000294:innervation / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D007545:Isoproterenol; D009842:Oligopeptides; D011433:Propranolol; D000092502:Renin Inhibitors; C034503:H 77