The ventrolateral medulla. A new site of action of the renin-angiotensin system.
High-affinity binding sites for angiotensin II (Ang II) in the ventrolateral medulla suggest that Ang II may act at cell groups that are known to modulate blood pressure. This hypothesis was investigated by the topical application of angiotensin I (Ang I), Ang II, the Ang II antagonist [Sar1, Thr8]Ang II, and the Ang I converting enzyme inhibitor MK 422 to a restricted region of the ventral medullary surface known as the glycine-sensitive area. Both Ang I (100 pmol) and Ang II (100 pmol) produced significant (p less than 0.01) increases in blood pressure (+20 +/- 4 and +31 +/- 5 mm Hg, respectively) that were associated with no change in heart rate. Furthermore, the relationship between the peak increases in blood pressure and Ang II was dose-dependent. Blockade of endogenous Ang II by [Sar1, Thr8]Ang II (13 nmol) produced a significant decrease in baseline blood pressure (-8 +/- 1 mm Hg; p less than 0.001). Similarly, topical application of MK 422 prevented the pressor effect of Ang I. Taken together, these experiments indicate that at least some components of the renin-angiotensin system exist in the ventrolateral medulla and they may modulate vasomotor outflow.
Andreatta
S H
SH
Department of Brain and Vascular Research, Cleveland Clinic Foundation, OH 44195.
Averill
D B
DB
Santos
R A
RA
Ferrario
C M
CM
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002415:Cats; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D006339:Heart Rate; D008526:Medulla Oblongata / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D015773:Enalaprilat