1 The e ects of ZD6169, a novel ATP-sensitive K + channel (K ATP channel) opener, were investigated on membrane currents in isolated myocytes using patch-clamp techniques. Tension measurement was also performed to study the e ects of ZD6169 on the resting tone of pig urethral smooth muscle. 2 Levcromakalim was more potent than ZD6169 in lowering the resting urethral tone. Relaxation induced by low concentrations of ZD6169 (43 mM) was completely suppressed by additional application of glibenclamide (1 mM). In contrast, glibenclamide (1 ± 10 mM) only partially inhibited the relaxation induced by higher concentrations of ZD6169 (510 mM). 3 Bay K8644 (1 mM) reduced the maximum relaxation produced by ZD6169 (510 mM). 4 In whole-cell con®guration, ZD6169 suppressed the peak amplitude of voltage-dependent Ba 2+ currents in a concentration-and voltage-dependent manner, and at 100 mM, shifted the steady-state inactivation curve of the voltage-dependent Ba 2+ currents to the left at a holding potential of 790 mV. 5 In cell-attached con®guration, open probability of unitary voltage-dependent Ba 2+ channels (27 pS, 90 mM Ba 2+ ) was inhibited by 100 mM ZD6169 and by 10 mM nifedipine. 6 Reverse transcriptase-polymerase chain reaction (RT ± PCR) analysis revealed the presence of the transcript of the a 1C subunit of L-type Ca 2+ channels in pig urethra. 7 These results demonstrate that ZD6169 causes urethral relaxation through two distinct mechanisms, activation of K ATP channels at lower concentrations and inhibition of voltagedependent Ca 2+ channels at higher concentrations (about 10 mM).
A 51-year-old man recently diagnosed with preclinical Cushing's syndrome complained of chest oppression concomitant with back pain. Following contrast-enhanced computed tomography (CT) to rule out acute aortic dissection, he developed chest symptoms accompanied by elevation of blood pressure to 240/120 mmHg and ischemic electrocardiographic change. Urgent coronary angiography revealed a coronary artery aneurysm (15 mm × 6 mm) in the distal portion of the left anterior descending artery concomitant with coronary flow delay. Re-analysis of the blood sample taken at admission showed elevated plasma catecholamine concentrations, leading to a diagnosis of paroxysmal pheochromocytoma. An adrenal tumor was excised laparoscopically and histologically shown to be a pheochromocytoma. These findings show that coronary artery aneurysm may be a rare complication of pheochromocytoma, and indicate that monitoring of blood pressure or analysis of stored blood samples, if necessary, is essential to detect pheochromocytoma when using contrast medium or glucagon in patients known to have an adrenal incidentaloma. It should be noted that pre-treatment with an ␣-blocker is necessary when patients who are likely to have pheochromocytoma need to undergo contrast-enhanced CT.
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