title: Separation of peripheral and central cardiovascular actions of angiotensin II.
abstract: The pressor and vasoconstrictor action of angiotensin II (ANG II) is considered to be caused by a combination of its direct and indirect vascular effects, the latter mediated by the sympathetic nervous system. The purpose of this study was to determine the extent to which the direct and indirect actions of ANG II contribute to its pressor and vascular effects. Blood pressure, cutaneous vascular, and plasma norepinephrine responses to intravenous ANG II were measured in conscious rabbits before and after inhibition of central sympathetic outflow with intravenous and intracisternal clonidine and after ganglionic blockade with intravenous pentolinium. Intravenous ANG II caused a similar dose-related rise in blood pressure before and after sympathetic blockade with intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. In contrast, the dose-related fall in cutaneous ear blood flow and cutaneous ear temperature and rise in cutaneous ear vascular resistance induced by intravenous ANG II were abolished after intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. Heart rate was unchanged after ANG II. There were no changes in back skin or rectal temperature. There was a nonsignificant fall in plasma norepinephrine and no change in epinephrine after ANG II. These results demonstrate that the acute pressor response to intravenous ANG II is mediated by its direct vascular effects and is not dependent on central or ganglionic stimulation of the sympathetic nervous system, in contrast to the effect of ANG II on cutaneous ear vasoconstriction, which is predominantly caused by a centrally mediated increase in sympathetic nervous activity. Our results separate, in conscious rabbits, the direct vascular effects of ANG II from its indirect vascular actions, which are mediated by central sympathetic stimulation in the brain.
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: J S
authors.initials: JS
authors.lastname: Kooner
authors.forename: C N
authors.initials: CN
authors.lastname: May
authors.forename: S
authors.initials: S
authors.lastname: Peart
authors.forename: C J
authors.initials: CJ
authors.lastname: Mathias
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D010425:Pentolinium Tartrate / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D012881:Skin Temperature / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000804:Angiotensin II; D010425:Pentolinium Tartrate; D003000:Clonidine; D009638:Norepinephrine