Angiotensin II evokes noradrenaline release from the paraventricular nucleus in conscious rats.
In vitro and in vivo experiments have provided indirect evidence that some of the central actions of angiotensin II (ANG II) involve catecholaminergic pathways in the brain. In this study in conscious rats we investigated the effect of stimulation of periventricular ANG II receptors on blood pressure and on catecholamine release (microdialysis and HPLC) from the paraventricular nucleus (PVN), a hypothalamic area thought to be instrumental in the central pressor responses to ANG II through the release of vasopressin into the blood. Intracerebroventricular (i.c.v.) injections of pressor doses of ANG II (1 ng and 100 ng) led to significant dose-dependent increases of the noradrenaline (NA) release in the PVN (1 ng: 30.95 +/- 6.01 to 47.38 +/- 6.79 pg/sample, P less than or equal to 0.01; 100 ng: 32.93 +/- 5.38 to 73.18 +/- 11.4 pg/sample, P less than or equal to 0.01). These changes coincided in extent and duration with the respective pressor responses. A subpressor dose of ANG II (100 pg) did not release catecholamines from the PVN. Dopamine (DA) and the NA and DA, metabolites 3,4-dihydroxyphenylethylglycol and 3,4-dihydroxyphenylacetic acid, were not influenced by i.c.v. injections of ANG II at any dose. Pretreatment with the novel non-peptide ANG II-AT 1 receptor antagonist DuP 753 (5 micrograms, i.c.v.) abolished the effect of 100 ng ANG II on blood pressure and on NA release. Our results show for the first time in vivo that stimulation of periventricular ANG II-AT 1 receptors induces a selective NA release in the PVN. They further support the hypothesis that ANG II engages a noradrenergic pathway in the PVN to release vasopressin.
Stadler
T
T
Department of Pharmacology, University of Heidelberg, F.R.G.
Veltmar
A
A
Qadri
F
F
Unger
T
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors
D015102:3,4-Dihydroxyphenylacetic Acid; D000804:Angiotensin II; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine