ANP AND BRADYCARDIAC REFLEXES IN HYPERTENSIVE RATS - INFLUENCE OF CARDIAC-HYPERTROPHY

In previous studies we demonstrated that in normotensive rats, but not in spontaneously hypertensive rats (SHR), atrial natriuretic peptide (ANP) enhances bradycardic reflexes through an action on cardiac vagal afferent pathways. The present study aimed to determine whether cardi ac hypertrophy, hypertension, or a nonreversible genetic factor accoun ted for the insensitivity of SHR to ANP action on cardiac reflex pathw ays. SHR were treated with the angiotensin-converting enzyme (ACE) inh ibitor perindopril (3 mg/kg per day) for 6 weeks from 4 to 9 weeks of age (SHR-S, n=10) or for 9 weeks from 4 to 12 weeks of age (SHR-L, n=1 0) or were untreated(SHR, n=10) to produce differential effects on blo od pressure and left ventricle/body weight ratio (LV/BW). Untreated no rmotensive Wistar-Kyoto rats (WKY, n=10) were also studied. At 13 week s of age, all rats were instrumented with aortic and jugular catheters , and at 14 weeks we measured heart rate reflexes to rapid intravenous infusions of methoxamine (100 mu g/kg, cardiac baroreflex) and seroto nin (5 to 60 mu g/kg,von Bezold-Jarisch cardiac chemosensitive reflex) , with either alpha-rat ANP (150 ng/kg per minute IV) or saline vehicl e (270 mu L/h IV) infusion. Perindopril treatment for 6-week (SHR-S) a nd 9-week SHR-L) durations maintained blood pressure at normotensive l evels in both groups. SHR-S exhibited a small degree of cardiac hypert rophy (LV/BW was 8% higher than in WKY but 11% less than in untreated SHR), but LV/BW was normalized in SHR-L (to within 1% of WKY LV/BW). I n WKY, ANP significantly (P<0.05) enhanced bradycardic responses to bo th the cardiac baroreflex (by 42+/-10%) and von Bezold-Jarisch chemose nsitive reflex (by 17+/-5%) activation bur had no effect in SHR. The c ardiac reflex action of ANP was restored in SHR-L (ANP enhanced reflex bradycardia by 28+/-12% and 36+/-8%, baroreflex and von Bezold-Jarisc h reflex, respectively; P<0.05), but SHR-S, which developed some cardi ac hypertrophy, remained unresponsive to ANP. Our results suggest that the inability of ANP to sensitize cardiac vagal (nonarterial) afferen ts in SHR was not due to an inherited irreversible component, or the h ypertension per se, but was associated with the presence of cardiac hy pertrophy. A functional consequence of hypertension-induced cardiac hy pertrophy may be the inhibition of the cardioprotective action of ANP through cardiac vagal reflexes.