Nitric oxide-dependent hypotensive effects of adrenomedullin in rats

✍ Scribed by Kazuki Matsunaga; Takanori Iwasaki; Yukio Yonetani; Kazuo Kitamura; Tanenao Eto; Kenji Kangawa; Hisayuki Matsuo

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 484 KB
• Volume: 37
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199601)37:1<55::aid-ddr4>3.0.co;2-l

✦ Synopsis

The association of nitric oxide (NO) with the hypotensive effects of adrenomedullin (AM) was investigated in anesthetized rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used at 11-13 weeks of age. Blood pressure and heart rate were measured from the femoral artery under mild anesthesia using pentobarbital. AM, over the dose range of 0.3-3 nmol/kg iv, produced dose-dependent sustained hypotension and compensatory tachycardia. These effects of AM at 0.3, 1, and 3 nmol/kg iv were significantly stronger in SHK (-9 ? 4, -53 ? 9, and -62 ? 7 mmHg) than in WKY (-4 ? 1, -16 I+_ 2, and -22 -C 2 mmHg). Those at 1 nrnol/kg iv were markedly inhibited in SHR (-53 to -19 mmHg) and in WKY (-16 to -12 mmHg) by treatment with the nitric oxide synthase (NOS) inhibitor NC-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv). O n the other hand, the difference of hypotensive effects in WKY and SHR by calcitonin gene-related peptide (CCRP) and the inhibitory effect by the treatment with L-NAME were smaller than seen with AM. These effects of CGRP at 0.03, 0.1, 0.3, and 1 nmol/kg iv were in S H R (-7 2 2, -18 ? 3, -42 ? 4, and -74 * 3 mmHg) and in WKY (-7 * 1, -16 f 1, -26 * 3, and -41 f 2 mmHg), respectively. Those at 0.3 nmol/kg iv were not significantly inhibited in SHR and in WKY (-26 to -20 mmHg) by treatment with L-NAME, 10 mg/kg iv. These results indicate that the A M hypotensive effect was more pronounced in the hypertensive state and strongly depends on N O synthesis.