title: Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide.
abstract: We have recently shown that hydrolysis of labeled angiotensin I in canine brainstem homogenate causes a rapid accumulation of the heptapeptide angiotensin-(1-7) [Ang-(1-7)]. Although this angiotensin fragment has no vasopressor activity, its consistent generation in brain homogenate led us to study its potential neurosecretory effects in the rat hypothalamo-neurohypophysial system (HNS) in vitro. Ang-(1-7) or angiotensin II (Ang II) was added to HNS perifusate in concentrations of 0.04, 0.4, and 4 microM, and release of arginine vasopressin (AVP) during each treatment was quantified as a percentage of the AVP release detected in the preceding collection period. Base-line release of AVP averaged 281 +/- 47 pg per 15 min (mean +/- SEM) in HNS explants (five experiments, five explants per chamber) perifused in Krebs solution at 37 degrees C, after a 1-hr equilibration period. At 0.04 microM, Ang II or Ang-(1-7) did not stimulate AVP release. Ang II increased AVP release over the control value by 172% +/- 44% and 268% +/- 66% at 0.4 and 4 microM, respectively; the same concentrations of Ang-(1-7) increased AVP release by 134% +/- 12% and 216% +/- 45%. The responses to Ang II and Ang-(1-7) at the highest concentration were both significant (P less than 0.05), and comparison by two-way analysis of variance indicated that Ang II and Ang-(1-7) were equipotent in stimulating AVP release over the range of concentrations studied. In the presence of the competitive Ang II antagonist [Sar1,Thr8]Ang II (20 microM), the release of AVP increased approximately equal to 2-fold. Neither Ang II nor Ang-(1-7) (4 microM) caused a further enhancement of AVP release in the presence of [Sar1,Thr8]Ang II. These data suggest that a hydrophobic residue in position 8 of the angiotensin peptide is not essential for activation of angiotensin receptors in the rat HNS. Moreover, the equipotence of Ang II and Ang-(1-7) indicates that Ang-(1-7) may participate in the control of AVP release.
authors: Department of Brain and Vascular Research, Cleveland Clinic Foundation, OH 44195.
authors: M T
authors: MT
authors: Schiavone
authors: R A
authors: RA
authors: Santos
authors: K B
authors: KB
authors: Brosnihan
authors: M C
authors: MC
authors: Khosla
authors: C M
authors: CM
authors: Ferrario
mesh_terms: D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000803:Angiotensin I; D012504:Saralasin; C118790:angiotensin I (1-7)