title: Contribution of angiotensin-(1-7) to blood pressure regulation in salt-depleted hypertensive rats.
abstract: We exposed 63 adult spontaneously hypertensive rats (SHR) and 10 (mRen-2)27 transgenic hypertensive rats to a 12-day regimen of either a normal diet (0.5%) or a low-salt diet (0.05%) to evaluate the hypothesis that the vasodepressor heptapeptide, angiotensin-(1-7) [Ang-(1-7)], buffers the pressor effects of angiotensin II during endogenous stimulation of the renin-angiotensin system. Catheters were inserted into a carotid artery and jugular vein under light anesthesia the day before the experiment. Separate groups of conscious instrumented SHR were given short-term infusions of an affinity-purified monoclonal Ang-(1-7) antibody or the neprilysin inhibitor SCH 39370. In addition, SHR and (mRen-2)27 rats were given the Ang-(1-7) receptor antagonist [D-Ala(7)]Ang-(1-7). Exposure to the low-salt diet increased plasma renin activity and elevated plasma levels of angiotensin I and angiotensin II in SHR by 81% and 68%, respectively, above values determined in SHR fed a normal salt diet. Concentrations of angiotensin I and angiotensin II were also higher in the kidney of salt-depleted SHR, whereas plasma and renal tissue levels of Ang-(1-7) were unchanged. Infusion of the Ang-(1-7) antibody produced dose-dependent pressor and tachycardic responses in salt-depleted SHR but no effect in SHR maintained on a normal-salt diet. A comparable cardiovascular response was produced in salt-depleted SHR given either SCH 39370 or [D-Ala(7)]Ang-(1-7). These agents had negligible effects on SHR fed a normal-salt diet. Blockade of Ang-(1-7) receptors produced a similar cardiovascular response in (mRen-2)27 transgenic hypertensive rats fed a low-salt diet. Injections of the heat-inactivated antibody or the subsequent infusion of the antibody to rats given [D-Ala(7)]Ang-(1-7) produced no additional effects. The data support the hypothesis that the hemodynamic effects of neurohormonal activation after salt restriction stimulate a tonic depressor action of Ang-(1-7).
authors.affiliation: Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Iyer
authors.forename: D B
authors.initials: DB
authors.lastname: Averill
authors.forename: M C
authors.initials: MC
authors.lastname: Chappell
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: A J
authors.initials: AJ
authors.lastname: Allred
authors.forename: C M
authors.initials: CM
authors.lastname: Ferrario
mesh_terms: D000704:Analysis of Variance; D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000502:physiology*; D001795:Blood Pressure Determination; D004039:Diet, Sodium-Restricted; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood
chemical_list: D004151:Dipeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D000804:Angiotensin II; C060631:Sch 39370; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7)