Angiotensin II sensitivity of afferent glomerular arterioles in endothelin-1 transgenic mice.
BACKGROUND
Although endothelin I (ET-1) is a very potent vasoconstrictor, ET-1 transgenic (ET-1 tg) mice are not hypertensive. This might be due to higher bioavailability of nitric oxide (NO) in ET-1 tg, which counteracts the effect of vasoconstrictors. We hypothesized lower angiotensin II (Ang II) sensitivity of afferent arterioles in ET-1 tg.


METHODS
Afferent arterioles were manually dissected and microperfused. Changes of the luminal diameter due to application of vasoactive substances were used for assessment of the reactivity of afferent arterioles. We investigated the effect of L-NAME, an unspecific NO synthase inhibitor, on basal tone, and the sensitivity of afferent arterioles to Ang II with and without pre-treatment with L-NAME. The renin-angiotensin-system was characterized by expression analysis of angiotensin-receptors and renin at the mRNA level.


RESULTS
L-NAME reduced afferent arterioles diameters similarly in ET-1 tg and wild-types (WT). Ang II sensitivity determined by calculation of EC50 for Ang II was less in ET-1 tg compared with WT (P<0.05). Ang II reduced luminal diameters to a lesser extent in ET-1 tg compared to WT (P<0.05). After pre-treatment with L-NAME, Ang II sensitivity and maximum constriction of afferent arterioles were similar in ET-1 tg and WT. The expression of renin- and Ang II-receptor-mRNA in the kidney did not differ between either group.


CONCLUSIONS
The loss of differences in the maximum constriction and Ang II sensitivity of afferent arterioles between ET-1 tg and WT in the absence of NO suggests pronounced NO effects in afferent arterioles of ET-1 tg. This might contribute to the maintenance of normal renal arteriolar tone in ET-1 tg mice.
Patzak
Andreas
A
Johannes-Müller-Institut für Physiologie, Humboldt-Universität zu Berlin, Universitätsklinikum Charité, Tucholskystr. 2, 10117 Berlin. andreas.patzak@charite.de
Bontscho
Julia
J
Lai
Enyin
E
Kupsch
Eckehardt
E
Skalweit
Angela
A
Richter
Claus-Michael
CM
Zimmermann
Mathias
M
Thöne-Reineke
Christa
C
Joehren
Olaf
O
Godes
Michael
M
Steege
Andreas
A
Hocher
Berthold
B
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000235:genetics; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012083:Renin / Q000096:biosynthesis / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester