Increased intracellular Na+ and depolarization favor angiotension tachyphylaxis in rabbit aorta.
Tachyphylaxis to both angiotensin II (ANG II) and Sar1-ANG II is observed in normal rabbit aorta rings, but helical strips show tachyphylaxis only to Sar1-ANG II, whereas everted rings are not tachyphylactic to either analogue. In normal rings, a good correlation was observed between intraluminal pH and degree of tachyphylaxis to both analogues, suggesting that rate-limiting access of the agonists to their site of action may enhance tachyphylaxis in this preparation. Membrane potential and intracellular Na+ activity measurements, as well as the relaxation by K+ of norepinephrine-contracted preparations in K(+)-free medium, indicated that helical strips are more depolarized than everted rings due to Na+ leakage into the smooth muscle cells. These results suggest that the differences in the degree of tachyphylaxis induced by angiotensin in different rabbit aorta preparations are due to a less accessible site of action in normal rings and to the higher intracellular Na+ and more depolarized state of helical strips relative to everted rings.
Frediani-Neto
E
E
Department of Biophysics, Escola Paulista de Medicina, Sao Paulo, Brazil.
Silva
E G
EG
Paiva
T B
TB
Paiva
A C
AC
D000804:Angiotensin II / Q000494:pharmacology; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D013618:Tachyphylaxis; D014661:Vasoconstriction
D000809:Angiotensins; D000804:Angiotensin II; D012964:Sodium; D011188:Potassium; D009638:Norepinephrine