Effects of veratridine on the action potentials and contractility of right and left ventricles from normo- and hypertensive rats.
1. We have studied the effects of prolonging the opening of sodium channels with veratridine on the action potentials (AP) and contractility of isolated right and left ventricles of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). It was examined whether the effects of veratridine were altered in the SHR right ventricle in the absence of hypertrophy. The main aim of the present study was to test the hypothesis that the effects of veratridine were altered in the SHR left ventricle in the presence of hypertrophy. 2. The tail-cuff pressures of 14- and 22-week-old, but not 5-week-old, SHR were greater than those of the WKY rat. At 14 weeks of age of SHR left, but not right, ventricle had developed hypertension-associated hypertrophy. 3. The AP and contractions and the ability of veratridine to prolong the AP and act as a positive inotrope were similar in the right ventricles from 22-week-old WKY rats and SHR. The effects of veratridine and the AP and contractions of left ventricles of 5-, 14- and 22-week-old WKY rats and of 5- and 14-week-old SHR were also similar. 4. The AP of the left ventricles of 22-week-old SHR were prolonged by 3 ms at the action potential duration (APD)50 and APD90 levels. The contractions to cardiac stimulation and the maximum combined force responses to cardiac stimulation and isoprenaline were reduced in the left ventricles of 22-week-old SHR compared with WKY rats and younger SHR. 5. The effectiveness of veratridine in prolonging the AP and augmenting the contractions to cardiac stimulation was reduced in the hypertrophied left ventricle of 22-week-old, but not 14-week-old, SHR. 6. In summary, the response to prolonging the opening of sodium channels with veratridine is not altered in the SHR right ventricle. However, in left ventricles of the hypertrophied 22-week-old, but not 14-week-old, SHR the effects of veratridine are reduced and this demonstrates that the response to prolonging the opening of sodium channels is changed in persistent hypertension-associated hypertrophy.
Nand
V
V
Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, New Zealand.
Doggrell
S A
SA
Barnett
C W
CW
D000200:Action Potentials / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014701:Veratridine / Q000494:pharmacology*
D000470:Alkaloids; D014701:Veratridine