title: Sensitivity of hypothalamic paraventricular nucleus to C- and N-terminal angiotensin fragments: vasopressin release and drinking.
abstract: We studied the effect of angiotensin (ANG) peptides and their C- and N-terminal fragments, microinjected bilaterally into the hypothalamic paraventricular nucleus (PVN) of male Wistar rats, on arginine vasopressin (AVP) release into the blood and drinking. ANG II (1-8) and the C-terminal ANG III (2-8) at 0.1-100 pmol/200 nl induced a dose-dependent increase in AVP release with a maximum of 26.45+/-6.0 and 31.86+/-7.0 pg/ml, respectively, vs 1.6+/-2.0 pg/ml in vehicle treated controls (P<0.001). The highest dose of ANG II and ANG III also induced drinking responses of 4.3+/-0.78 and 2.91+/-0.54 ml water/15 min, respectively. Bilateral pretreatment of the PVN with the AT1 receptor antagonist losartan (4 nmol/200 nl) inhibited ANG II- and ANG III-induced AVP release and drinking. Different doses of the C-terminal ANG IV (3-8), ANG (4-8) or ANG (5-8) peptides did not induce AVP release or drinking. The N-terminal ANG (1-7) peptide induced a dose-dependent increase in AVP release (maximum 8.5+/-3.5 pg/ml after 100 pmol) but the effect was much less potent than that induced by the same dose of ANG II or ANG III. ANG (1-7) failed to induce a drinking response. Pretreatment of the PVN with losartan or the AT2 receptor antagonist, PD 123177 (4 nmol/200 nl), inhibited the 100 pmol ANG (1-7)-induced AVP release. The N-terminal ANG (1-4) peptide did not affect AVP release or drinking at any dose tested. Our data demonstrate that the C-terminal ANG II (1-8) and ANG III (2-8), but not shorter fragments, can induce AVP release and drinking response via AT1 receptors in the PVN. The N-terminal ANG (1-7) was less potent in stimulating AVP release than ANG II or ANG III and had no influence on drinking. Thus, the presence of both arginine2 and phenylalanine8 in the angiotensin peptide sequence appears to be important to elicit AVP release and drinking from the PVN in vivo.
authors.affiliation: Institute of Pharmacology, University of Kiel, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Qadri
authors.forename: A
authors.initials: A
authors.lastname: Wolf
authors.forename: T
authors.initials: T
authors.lastname: Waldmann
authors.forename: W
authors.initials: W
authors.lastname: Rascher
authors.forename: T
authors.initials: T
authors.lastname: Unger
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D004327:Drinking Behavior / Q000187:drug effects*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000187:drug effects
chemical_list: D010446:Peptide Fragments; D000804:Angiotensin II; D001127:Arginine Vasopressin