[Modulatory effects of endothelin on carotid baroreflex in anesthetized rats]

Modulatory effects of endothelin (ET) on carotid baroreflex were examined in 27 anesthetized rats with isolated carotid sinus perfusion. The results obtained were as follows: (1) By perfusing with 1 nmol/L ET-1, the functional curve of carotid baroreflex (FCCB) was shifted to the left and downward with an increase in its peak slope (PS) from 0.40 +/- 0.02 to 0.51 +/- 0.02 kPa/kPa (P < 0.01), while the reflex decrease of mean arterial pressure (RD) was increased from 5.66 +/- 0.23 to 6.76 +/- 0.22 kPa (P < 0.01). The above results indicated that this dose of ET-1 facilitated the carotid baroreflex. (2) On the contrary, by perfusing with 10 nmol/L of ET-1, FCCB was shifted to the right and upward with a decrease of PS to 0.28 +/- 0.01 kPa/kPa (P < 0.01), while RD was decreased to 4.16 +/- 0.19 kPa (P < 0.01). In response to perfusion with 100 nmol/L ET-1, FCCB was further shifted to the right and upward with a marked decrease of PS to 0.19 +/- 0.03 kPa/kPa (P < 0.001), and RD was conspicuously decreased to 3.33 +/- 0.38 kPa (P < 0.001). These results showed that ET-1 at the doses of 10 or 100 nmol/L exerted an inhibitory action on baroreflex. (3) Selective ETA receptor blocker BQ123 (0.15 mumol/L) might abolish the effects of ET-1 (10 nmol/L) on baroreflex. (4) Preperfusing with KATP channel antagonist glibenclamide (10 mumol/L) could also eliminated the effects of ET-1. Taken together, it is suggested that ET-1 exerts a dual effects on baroreflex, being facilitatory at lower dose and inhibitory at higher dose. The latter effect is mediated by ETA receptor, in which KATP channels may be involved.