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Effects of adrenomedullin on cardiovascular system

หน่วยงาน จุฬาลงกรณ์มหาวิทยาลัย

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ชื่อเรื่อง : Effects of adrenomedullin on cardiovascular system
นักวิจัย : Supathra Amatyakul
คำค้น : Isolation perfusion (Physiology) , Adrenomedullin , Cardiovascular system , Rats
หน่วยงาน : จุฬาลงกรณ์มหาวิทยาลัย
ผู้ร่วมงาน : Suthiluk Patumraj , Hideyuki, Niimi , Chulalongkorn University. Graduate School
ปีพิมพ์ : 2542
อ้างอิง : 9743338357 , http://cuir.car.chula.ac.th/handle/123456789/9308
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Thesis (Ph.D.)--Chulalongkorn University, 1999

Adrenomedullin (AM) is a 52 amino acid peptide that was originally discovered in pheochromocytoma tissue. The role of AM as a hypotensive peptide and a potent vasodilator has been reported. However, the nature of the mechanism through which AM exerts its vasoactive property is going on the investigation. The present study was conducted to approach the physiological relevance of AM especially on the cardiovascular system and to clarify the possibility of mechanism that involve to the effect of AM on coronary vasodilation. The three different experimental models were used in this study. The study was performed in male Wistar rat weighing 200-300 g. In the whole body model, the intravenous administration of AM (1 nmol/kg BW) produced a transient decrease in mean arterial pressure (MAP). This reduction was rapid in onset and reached its peak within 30 seconds (MAP decreased by 29.86+-3.31 mmHg, p<0.001) and returned to its basal level within half an hour. However there was no change in heart rate. Peripheral vasodilation was suggested to involve in this hypotensive effect of AM. Therefore, the dorsal skinfold chamber model was used in order to make further evaluation of the effect of AM on peripheral circulation. Topical application of AM (10 -7 M) on the skin microcirculation produced significant arteriolar dilation at 3 minute after the application (from 56.80+-2.08 mum to 59.60+-2.80 mum and 35.00+-3.83 mum to 40.40+-5.49 mum for the second-order and the third-order arteriole, respectively; p<0.05). The result revealed the peripheral vasodilatory effect of AM. Finally, the main protocol of isolated perfused rat heart model was used in order to assess the biological responses of both cardiac performance and coronary circulation to AM. In addition, the possible mechanism (s) of AM on coronary vasodilation was also employed in this model. When a bolus dose of AM (20 mug) was injected into the heart via an aortic cannulation, cardiac contraction (+dp/dtmax) and cardiac relaxation (-dp/dtmax) decreased (+dp/dtmax : from 1740+-78 mmHg/sec to 1678+-89 mmHg/sec, p<0.05; -dp/dtmax : from 941+-55 mmHg/sec to 897+-62 mmHg/sec, p<0.05) at 5 minute after the administration of AM. Whereas heart rate (HR) and coronary blood flow (CBF) increased (HR : from 278+-6 beats/min to 305+-9 beats/min at 5 min after AM injection, p<0.01; CBF: from 7.00+-0.27 ml/min to 8.32+-0.29 ml/min at 3 min after AM injection, p<0.001). Electrocardiogram and ventricular cAMP production of the isolated perfused rat heart was not affected by a bolus injection of AM. The coronary vasodilation was attenuated after endothelium degradation by Triton X-100 (CBF increased by 15.70+-0.91% in endothelium-intact, by 4.64+-1.50% in endothelium-damage, p<0.001). Continuous infusion of L-NNA, nitric oxide synthase inhibitor; glibenclamide, an inhibitor of KATP channels; but not indomethacin, an inhibitor of cyclooxygenase pathway, attenuated the coronary vasodilator response to AM (CBF increased by 18.93+-1.42% in AM alone group, by 14.90+-1.22% in AM+L-NNA group, p<0.05 and by 5.46+-0.67% in AM+glibenclamide group, p<0.001). It is concluded that the coronary vasodilator response to AM is major mediated through the endothelium-dependent pathway. For which the mechanisms were expressed through the release of nitric oxide from the endothelium and the activation of KATP channels on endothelium and vascular smooth muscle.

บรรณานุกรม :
Supathra Amatyakul . (2542). Effects of adrenomedullin on cardiovascular system.
    กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย.
Supathra Amatyakul . 2542. "Effects of adrenomedullin on cardiovascular system".
    กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย.
Supathra Amatyakul . "Effects of adrenomedullin on cardiovascular system."
    กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย, 2542. Print.
Supathra Amatyakul . Effects of adrenomedullin on cardiovascular system. กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย; 2542.