NITRIC OXIDE-DEPENDENT HYPOTENSIVE EFFECTS OF ADRENOMEDULLIN IN RATS

The association of nitric oxide (NO) with the hypotensive effects of a drenomedullin (AM) was investigated in anesthetized rats. Spontaneousl y hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) wer e used at 11-13 weeks of age. Blood pressure and heart rate were measu red 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 A M at 0.3, 1, and 3 nmol/kg iv were significantly stronger in SHR (-9 /- 4, -53 +/- 9, and -62 +/- 7 mmHg) than in WKY (-4 +/- 1, -16 +/- 2, and -22 +/- 2 mmHg). Those at 1 nmol/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 N-G-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv). On the other hand, the difference of hypo tensive effects in WKY and SHR by calcitonin gene-related peptide (CGR P) 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 nmo l/kg iv were in SHR (-7 +/- 2, -18 +/- 3, -42 +/- 4, and -74 +/- 3 mmH g) and in WKY (-7 +/- 1, -16 +/- 1, -26 +/- 3, and -41 +/- 2 mmHg), re spectively. Those at 0.3 nmol/kg iv were not significantly inhibited i n SHR (-42 to -43 mmHg) and in WKY (-26 to -20 mmHg) by treatment with L-NAME, 10 mg/kg iv. These results indicate that the AM hypotensive e ffect was more pronounced in the hypertensive state and strongly depen ds on NO synthesis. (C) 1996 Wiley-Liss, Inc.