We tested the hypothesis that the atrial natriuretic peptide (ANP) mediated decrease in baroreceptor sensitivity that is seen in normal rats is more pronounced in a state of depressed cardiac performance. Holtzman rats (n = 15) were injected with Adriamycin (1 mg/kg i.p. 3 times/week for 8–10 weeks). Control rats (n = 17) were injected with 0.9% saline. Experiments were done in conscious animals that had been catheterized for i.v. infusions and for measurement of arterial blood pressure (ABP) and heart rate (HR). ANP (250 ng∙kg−1∙min−1) or saline vehicle was infused i.v. Graded periodic bolus injections of phenylephrine or sodium nitroprusside were given to assess baroreceptor sensitivity (beats∙min−1∙mmHg−1) up to 60 mmHg (1 mmHg = 133.3 Pa) above and below resting ABP. The following day the experiment was repeated with the ANP–vehicle regimen reversed. Finally, the rats were anesthetized and the rate of left ventricular pressure increase (dP/dt) was measured. Data evaluation included calculation of least squares linear regression slopes of peak ΔHR vs. peak ΔABP, applying corrections for experimental errors in both the dependent and independent variables. Adriamycin rats (A) did not differ significantly from control rats (C) with respect to either initial ABP (A = 105 ± 5; C = 100 ± 3; mean mmHg ± SEM) or initial HR (335 ± 9 vs. 312 ± 13 beats∙min−1). However, their indices of cardiac performance were significantly depressed. The maximum rates of left ventricular pressure increase, +dP/dtmax, were A = 2877 ± 108 and C = 4569 ± 223 mmHg/s (p < 0.0001) and the maximum rates of decrease, −dP/dtmin, were A = −2459 ± 52 and C = −4076 ± 287 mmHg/s (p < 0.0001). Adriamycin-treated rats also showed significantly depressed baroreceptor sensitivity. This was particularly marked during blood pressure decreases in the presence of ANP. In this experimental setting, transient decreases in ABP resulted in physiologically inappropriate bradycardia. The results suggest that elevated plasma levels of ANP may have detrimental effects on mechanisms of cardiovascular compensation during heart failure.Key words: baroreflex, blood pressure regulation, adriamycin.
A genetic variant of the atrial natriuretic peptide gene is associated with left ventricular hypertrophy in a non-diabetic population – the Malmö preventive project study
