Neuropeptide Y/angiotensin II interactions in central cardiovascular regulation of the rat.
Neuropeptide Y (NPY)/angiotensin II (ANG II) interactions have been studied in the central nervous system of the rat in view of their co-distribution and their opposing role in central cardiovascular control using quantitative receptor autoradiography and measurements of mean arterial blood pressure (MAP), heart rate and respiratory rate. The receptor autoradiographical experiments show that incubation with ANG II (10 nM) produces an increase in porcine (p) iodinated NPY-(1-36) [125I]pNPY-(1-36) binding within the dorsal strip (ds) of the nucleus tractus solitarius (nTS). Immunocytochemical analysis of intracisternally injected ANG II indicated that it could reach this area, in addition to the periventricular gray of the medulla oblongata, the pons and the periventricular part of the dorsal thalamus and dentate gyrus. Furthermore, a threshold dose of ANG II given intracisternally (3 nmol/rat) together with a dose (75 pmol/rat) of pNPY-(1-36) close to its ED50 value for reducing MAP, not only counteracts the vasodepressor action of pNPY-(1-36) but also leads to a marked increase of MAP. Also the bradycardic and bradypneic actions of pNPY-(1-36) are counteracted by this dose of ANG II. In contrast, a threshold dose of pNPY-(1-36) does not counteract the pressor action of an ED50 dose of ANG II (10 nmol/rat) but even enhances the peak pressor action of ANG II. These results may be explained on the basis that central ANG II receptor activation leads to an uncoupling of the NPY Y1 receptor, which mediate the vasodepressor action of pNPY-(1-36) and which is preferentially labeled by [125I]pNPY-(1-36).(ABSTRACT TRUNCATED AT 250 WORDS)
Aguirre
J A
JA
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Fuxe
K
K
Hedlund
P
P
Narváez
J A
JA
Cintra
A
A
Rosén
L
L
Agnati
L F
LF
D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects
D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D011945:Receptors, Angiotensin; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; D000804:Angiotensin II