Spinal noradrenergic pathways and pressor responses to central angiotensin II.
We have investigated the contribution of spinal noradrenergic (NA) pathways to the central pressor effects of angiotensin II (ANG II) in conscious rabbits with intact baroreceptors and after sinoaortic denervation (SAD). Very low intracisternal (ic) doses of ANG II [half maximum dose (ED50) = 6 x 10(-15) mol] produced increases in mean arterial pressure (MAP) and decreases in heart rate. Pressor responses to intracisternal ANG II were markedly reduced by 100 pmol of the ANG II antagonist [( Sar1, Ile8] ANG II, ic) and by intravenous prazosin, suggesting that central activation of ANG II receptors increased sympathetic vasoconstrictor tone. After SAD, the rabbits exhibited a 900-fold increase in sensitivity to ANG II (i.e., responded to very much lower doses, ED50 = 5 x 10(-18) mol). Intraspinal 6-hydroxydopamine (6-OHDA) injections given 1 mo earlier did not alter dose-response curves in baroreceptor-intact rabbits. However, the SAD-induced increase in sensitivity to ANG II was not observed in rabbits with depletion of spinal NA pathways. The results suggest intracisternal administration of ANG II activates two functionally distinct pathways: 1) a very sensitive site that utilizes NA projections to the spinal cord, and 2) a less sensitive site that uses non-NA descending pathways. Under normal baroreceptor input the former pressor pathway is completely inhibited. Thus the role of the central renin-angiotensin system may be of greater physiological importance in conditions where the baroreflex is suppressed.
Elghozi
J L
JL
Baker Medical Research Institute, Prahran, Victoria, Australia.
Head
G A
GA
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001696:Biomechanical Phenomena; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002946:Cisterna Magna; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D007267:Injections; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D011817:Rabbits; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology*
D001679:Biogenic Amines; D006892:Hydroxydopamines; D000804:Angiotensin II; D016627:Oxidopamine; D009638:Norepinephrine