Angiotensin-(1-7) modulates vascular resistance and sympathetic neurotransmission in kidneys of spontaneously hypertensive rats.
OBJECTIVE
Angiotensin (Ang)-(1-7) generated from Ang I and II is reported to act as an endogenous angiotensin-converting enzyme (ACE) inhibitor and angiotensin type 1 (AT1)-receptor antagonist in vitro and in vivo. Ang-(1-7) has been suggested to play an important role in hypertension.


RESULTS
Therefore, we tested whether Ang-(1-7) differentially modulates vascular resistance and neurotransmission in isolated kidneys of spontaneously hypertensive rats stroke prone (SHR-SP) and Wistar-Kyoto rats (WKY). Ang-(1-7) was administered in three concentrations (0.1, 1 and 10 micromol/l) to prevent Ang I- and Ang II-induced pressor responses and facilitation of noradrenaline release. There were indeed concentration-dependent strain differences. Ang-(1-7) prevented Ang I- and Ang II-mediated changes in vascular resistance more potently in SHR-SP than in WKY by inhibiting ACE and by blocking AT1-receptors. Ang-(1-7) by itself had no influence on renal vascular tone in both strains. Ang-(1-7) inhibited Ang I-mediated facilitation of noradrenaline release more potently than Ang II-mediated facilitation of noradrenaline release. Ang-(1-7) by itself enhanced noradrenaline release from SHR-SP, but not from WKY kidneys.


CONCLUSIONS
Ang-(1-7) had a greater impact on Ang I and Ang II modulation of renal vascular resistance in SHR-SP than in normotensive rats. Furthermore, Ang-(1-7) by itself has facilitatory presynaptic effects on noradrenaline release but no postsynaptic effects on renal vascular resistance in SHR-SP. Since plasma levels of Ang-(1-7) accumulate during ACE-inhibitor or AT1-receptor antagonist therapy, Ang-(1-7) could contribute to antihypertensive effects of these agents.
Stegbauer
Johannes
J
Department of Internal Medicine I, Marienhospital Herne, Ruhr-University Bochum, Hölkeskampring 40, D-44625 Herne, Germany.
Oberhauser
Vitus
V
Vonend
Oliver
O
Rump
Lars Christian
LC
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D009638:Norepinephrine