Summary The increase in norepinephrine (NE) blood levels in human heart failure correlates with prognosis. In this study, we determined whether continuous NE infusion alters the positive inotropic and chronotropic responses of isolated rat cardiac muscles. Osmotic mini-pumps were implanted subcutaneously (s.c.) in 43 adult male rats to deliver NE (160 μg/kg/h for 14 days); 42 rats were sham-operated. Isolated left and right atria and left and right ventricular (LV, RV) papillary muscles were prepared to measure positive inotropic or chronotropic responses to NE, phenylephrine, forskolin, dibutyryl cyclicAMP (dbcyclicAMP), and calcium chloride. NE infusion caused (a) a 22% increase in LV wet weight without altering atrial or RV wet weights; (b) an 18% decrease in maximal inotropic response to calcium chloride in LV papillary muscles only; (c) a significantly decreased peak response to NE [72 ± 5 vs. 93 ± 5% (sham rats) of calcium chloride] but not to forskolin or dbcyclicAMP in RV papillary muscles; (d) an increased incidence of ectopy at low concentrations of NE, forskolin, and dbcyclicAMP in LV papillary muscles; (e) no alteration in papillary muscle responses to phenylephrine but significantly increased left atrial inotropic responses [51 ± 5 vs. 33 ± 2% (sham rats) of calcium chloride] and right atrial chronotropic responses [30 ± 2 vs. 18 ± 4 (sham rats) beats/ min]; and (f) a selective decrease in β1-adrenoceptor density in both ventricles. Thus, NE infusion causes selective LV hypertrophy; responses of compounds that increase intracellular cyclicAMP are affected to a greater extent in papillary muscles from the hypertrophied ventricle than in tissues from the other chambers of the heart.

1. The positive inotropic and chronotropic responses to adrenoceptor agonists (noradrenaline, phenylephrine), to compounds which increase cAMP by post-adrenoceptor mechanisms (forskolin, theophylline and dibutyryl cAMP) and to calcium chloride were measured in isolated rat atria and papillary muscles from both ventricles. 2. Noradrenaline produced similar maximal inotropic responses to calcium chloride in all tissues. Forskolin gave similar responses to calcium chloride in atrial but not ventricular tissues; the reverse was observed with dibutyryl cAMP. Phenylephrine and theophylline produced significantly smaller inotropic responses than calcium chloride in all tissues, especially in ventricular tissues. 3. Maximal chronotropic responses to noradrenaline, theophylline and dibutyryl cAMP were similar. Forskolin produced significantly greater responses while calcium chloride and phenylephrine produced significantly smaller responses than noradrenaline. 4. These results show that the maximal positive inotropic response of some agonists is markedly dependent on the tissue chosen. Further, chronotropic responses in right atria do not mimic inotropic responses in left atria.

SUMMARY1. The relationship between left ventricle‐to‐body weight ratio (LV/BW), mean arterial pressure (MAP, the average of 12 h of intra‐arterial monitoring in conscious animals) and plasma renin activity (PRA) was assessed at 12 weeks after unilateral clipping or sham operation in twenty‐four one‐kidney rats and twenty‐six two‐kidney rats.2. The degree of hypertension and left ventricular hypertrophy were similar in one‐kidney and two‐kidney groups. There was a close linear relationship between LV/BW and MAP which was similar in one‐kidney and two‐kidney rats.3. PRA was significantly elevated only in two‐kidney rats and was not related to the degree of hypertrophy after accounting for the effect of PRA on MAP.4. These data suggest that activation of the renin‐angiotensin system does not contribute directly to myocardial hypertrophy in rats with renal‐clip hypertension.