Observations on atrial natriuretic peptide, sympathetic activity and renal Ca2+ pump in diabetic and hypertensive rats

Abstract

The relationship between atrial natriuretic peptide (ANP) and peripheral sympathetic nervous system function was studied in diabetic and hypertensive rats. Animals were studied in diabetic and hypertensive rats. Animals were divided into four groups: control, diabetic, hypertensive and diabetic plus hypertensive. Diabetes was induced by streptozotocin (65 mg/kg) injection and hypertension by abdominal aortic constriction. Studies were performed at 1 and 6 weeks. Plasma ANP was increased at 1 week in all groups except controls. Noradrenaline turnover, an index of sympathetic activity in kidney, was attenuated in all pathological groups unlike controls. These changes were associated with increased activity of Ca2++Mg2+ ATPase, which is known to serve as a Ca2+ pump in kidney cortex basolateral membrane. In contrast, at 6 weeks, Ca2++Mg2+ ATPase was significantly decreased only in the diabetic plus hypertensive group which also showed signs of congestive heart failure, increased sympathetic activity and decreased plasma ANP levels. Intracerebral microdialysis of the extracellular space around the paraventricular nucleus (PVN) of the hypothalamus showed a decreased concentration of ANP in the diabetic plus hypertensive group. Infusion of ANP and pentolinium, a ganglionic blocker in diabetic plus hypertensive Ca2+ restored pump activity towards control values; ANP alone had no effect. Our results indicate decreased plasma ANP levels, increased sympathetic drive and a depressed kidney Ca2+ pump in diabetic plus hypertensive rats with heart failure. The relationships between these factors, and the potential modulating role of ANP is discussed.