Postnatal development of vascular resistance of the rabbit isolated perfused kidney: modulation by nitric oxide and angiotensin II.
Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II (AII)-induced vasoconstrictions. Kidneys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10(-5) M indomethacin. RVR decreased with age from 12.7 +/- 0.6 at 1 wk to 10.1 +/- 0.5 mm Hg min g mL-1 at 6 wk. N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10(-8) M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10(-10) M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postnatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.
Simeoni
U
U
Laboratoire de Pharmacologie Physiologie Réno-vasculaire (CJF INSERM 9409), Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Zhu
B
B
Muller
C
C
Judes
C
C
Massfelder
T
T
Geisert
J
J
Helwig
J J
JJ
D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester