Increased intracellular Na+ and depolarization favor angiotension tachyphylaxis in rabbit aorta

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Frediani-Neto, Eugenio [UNIFESP]
Silva, Eneida de Gusmão [UNIFESP]
Paiva, Therezinha Bandiera [UNIFESP]
Paiva, Antonio Cechelli de Mattos [UNIFESP]
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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.
American Journal Of Physiology-heart And Circulatory Physiology. Bethesda: Amer Physiological Soc, v. 260, n. 2, p. H373-H378, 1991.