INVOLVEMENT OF β-ADRENOCEPTORS IN THE MODULATION OF BAROREFLEX BY SK CHANNELS IN NUCLEUS TRACTUS SOLITARII OF THE RAT

• Main Authors: Cheng Ming-Hong, 鄭明宏
• Other Authors: Yen Jiin-Cherng
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/03534064692065465397

碩士 === 國立陽明大學 === 藥理學研究所 === 90 === Small conductance, calcium-activated potassium (SK) channels are widely distributed in the central nerves system. Microinjection of apamin into the nucleus tractus solitarii (NTS) potentiates the baroreflex response (BRR) in the Sprague-Dawley (SD) rat. This may reflect that SK channels play a crucial role in the modulation of baroreflex response. Furthermore, hypertension and acute myocardial infarction are always associated with sympathetic hyperactivity and impairment of BRR in animal and clinical experiments. Treatment with β-adrenoceptor blockers significantly decreases sympathetic activity and patients mortality. However the relationship between sympathetic activity reduction and BRR improvement has remained unclear. Using direct application of drugs through microinjection and power spectral analysis of cardiovascular parameters including systemic arterial pressure (SAP)、heart rate (HR) and BRR in two commonly used strains of rat, viz., the SD and Wistar-Kyoto (WKY) rats, the present study aimed at investigating the possible involvement of adrenoceptors in the modulation of baroreflex by SK channels in the NTS of the rat. Experiments were conducted under pentobarbital anesthesia, cardiovascular parameters were monitored through a femoral artery cannula, the low-frequency component (BLF) of SAP was regarded as an index of sympathetic activity, BRR was estimated from changes in the gain of blood pressure response to intravenous injection of the α-adrenoceptor agonist phenylephrine. The results indicated that bilateral microinjection of apamin (0.5-50 pmol/50 nl), a selective inhibitor of SK channels, into the NTS significantly potentiated BRR in the SD rat, but attenuated it in the Wistar-Kyoto (WKY) rat, while elevating BLF in both strains. Intravenous pretreatment with propranolol (1-2 mg/kg), a non-selective β-adrenoceptor blocker, prior to microinjection of apamin had no effects on the SD rat, but antagonized the BRR attenuation and BLF elevation in the WKY. Intravenous pretreatment with the β-1 selective adrenoceptor blocker atenolol (1 mg/kg) had no effects on the WKY, but potentiated the BRR and suppressed BLF in the SD. Further, co-microinjection with apamin and propranolol (100 pmol/50 nl) into the NTS antagonized the BRR potentiation and enhanced BLF elevation in the SD and reversed the BRR attenuation to potentiation and enhanced BLF elevation in the WKY. Co-microinjection with selective β-1 (metoprolol, 100 pmol/50 nl) or selective β-2 (ICI 118,551, 100 pmol/50 nl) adrenoceptor blockers both antagonized the BRR potentiation and BLF elevation in the SD and reversed the BRR attenuation to potentiation in the WKY. But metoprolol was strengthen BLF seems ICI 118,551 was not in the WKY. Co-microinjection of apamin and the non-selectiveα-adrenoceptor blocker (phentolamine, 100 pmol/50 nl) into the NTS significantly attenuated the BRR potentiation and BLF elevation in the SD, reversed the BRR attenuation to potentiation and elicited a biphasic response in BLF of initial elevation followed by attenuation in the WKY. We suggest that SK channels modulated BRR via inactivation of α- or β-adrenoceptors within the NTS and play a distinct role between different strains of rats. Furthermore, SK channels may modulate BRR without altering the sympathetic outflow.