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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.

To determine whether there are differences in cardiac beta-adrenoceptor responsiveness, isoprenaline affinity constants and fractional beta-adrenoceptor occupancy-response relationships for isoprenaline in the early stages of established hypertension, we studied the effects of bromoacetylalprenololmenthane (BAAM) and ([3,5-diamino-6-chloro-N-(1[N-beta-(2-hydroxyl-3-alpha-naphthoxypropy lamino)ethylcarbamoyl]-1-methylethyl)-pyrazine-2-carboxamide (ICI 147 798), slowly reversible beta-adrenoceptor antagonists, on the isoprenaline responses of the left ventricular papillary muscle and the left and right atria of 6-month-old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The papillary muscles, but not the right and left atria, of the SHR were less responsive to isoprenaline than those of the WKY. The isoprenaline pD2 values (the negative logarithms of the molar concentrations of agonist producing 50% of the maximum response) were 7.72 and 8.00 on the SHR and WKY papillary muscles, respectively. On the WKY papillary muscle the isoprenaline KA values were 2-3 x 10(-6) M, which is as expected for isoprenaline at beta1 or beta2-adrenoceptors. Isoprenaline had 100-fold greater affinity on the WKY and SHR left atria than on the papillary muscles; the isoprenaline KA values were 2-4 x 10(-8) M. On the WKY papillary muscle and left atrium, isoprenaline had to occupy 3-4% of the beta-adrenoceptors to produce a 50% maximum response; on the WKY papillary muscle and left atrium isoprenaline had to occupy 25-35% and 55%, respectively, of the beta-adrenoceptors to produce a 90% maximum response. The SHR papillary muscles and left atrium had smaller beta-adrenoceptor reserves for isoprenaline than did the WKY tissues. We were unable to obtain isoprenaline KA values on the WKY right atrium. The isoprenaline KA value on the SHR right atrium was 1-4 x 10(-8) M. Because the isoprenaline KA values for the left and right atria are markedly different from those previously reported for isoprenaline at beta1 or beta2-adrenoceptors, we suggest that atypical beta-adrenoceptors might be present on the atria of WKY and SHR. We have also demonstrated a lower beta-adrenoceptor reserve on SHR papillary muscle and atria in the early stages of established hypertension.