Antihypertensive action of amiodarone in spontaneously hypertensive rats.
The antihypertensive effect of amiodarone was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The SHR and WKY were treated with amiodarone (1 mg/mL PO) or tap water (control) for 20 weeks. The indirect arterial pressure (AP) was monitored weekly using the tail-cuff method. At the end of the 20th week, the direct AP was measured, and the systolic AP and pulse interval time series were submitted to autoregressive spectral analysis. In addition, cardiac baroreflex sensitivity and left ventricular weight were evaluated as well. The indirect AP was reduced 1 week after the beginning of amiodarone treatment. The direct mean AP and pulse interval were, respectively, 135+/-8 mm Hg and 191+/-3 ms in SHR treated with amiodarone (187+/-8 mm Hg and 156+/-7 ms in control SHR, P<0.05) and 87+/-3 mm Hg and 207+/-8 ms in WKY treated with amiodarone (105+/-8 mm Hg and 174+/-4 ms in control WKY, P<0.05). In SHR treated with amiodarone, the low-frequency oscillations of AP were lower (8.5+/-1.2 mm Hg(2) versus 14.4+/-2.9 mm Hg(2) in control SHR, P<0.05), whereas the reflex bradycardia was higher (0.84+/-0.12 ms/mm Hg versus 0.32+/-0.22 ms/mm Hg in control SHR, P<0.05). The left ventricle weight was also smaller in SHR treated with amiodarone (2.94+/-0.12 mg/g versus 3.45+/-0.24 mg/g in control SHR, P<0.05). In WKY, amiodarone induced similar changes as in SHR, except for a lack of effect in the left ventricle weight. These data indicate that amiodarone has an antihypertensive action in SHR that is associated with a reduction in vasomotor sympathetic modulation, an increase in vagal cardiac baroreflex sensitivity, and a decrease in cardiac hypertrophy.
Dias Da Silva
V J
VJ
Department of Biological Sciences, School of Medicine of Triângulo Mineiro, Uberaba, MG, Brazil. valdo@mednet.com.br
Cavalcante Viana
P C
PC
de Melo Alves
R
R
Salgado
H C
HC
Montano
N
N
Fazan
R
R
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000503:physiopathology / Q000517:prevention & control; D003971:Diastole; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012018:Reflex / Q000187:drug effects; D013599:Systole; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000638:Amiodarone