Systemic and regional vascular effects of atrial natriuretic peptide in a rat model of chronic heart failure

Abstract

To characterize the systemic and regional vascular effects of atrial natriuretic peptide (ANP) in chronic heart failure, central hemodynamics, regional blood flow and plasma ANP levels were determined in a rat model of myocardial infarction and failure and in sham-operated animals. Measurements were made in the conscious state before and after intravenous rANP [99-126] (8 micrograms bolus followed by continuous infusion of 1.0 microgram/kg/min). With this protocol, ANP significantly decreased cardiac output, right atrial, left ventricular end-diastolic and arterial pressures and there were increases in heart rate, systemic and intestinal vascular resistances in sham animals. Renal blood flow per gram of tissue was unchanged with ANP, but when expressed as a percentage of cardiac output, increased significantly, indicating a preferential renal vasodilatory effect of ANP. In rats with infarction and failure, this dose did not alter cardiac output or arterial pressure, but decreased right atrial and left ventricular blood flow. Although significantly reduced as compared to the control group, renal blood flow was not improved with ANP in the heart failure group. ANP plasma levels of the heart failure group were elevated at baseline (p less than 0.01), and increased 5-10 times after infusion of rANP. Thus, in rats with chronic heart failure, the renal vascular effects of ANP are blunted, which may, in part, explain the failure of ANP to restore the altered volume homeostasis in heart failure despite elevated ANP plasma levels. However, the effects on venous return were preserved which, in turn, improved cardiac performance via a reduction of preload.

Nitric Oxide-Mediated Vasodilatory Effect Of Atrial Natriuretic Peptide In Forearm Vessels Of Healthy Humans

“…Hirooka et al 23 examined the question of whether there is a difference in the direct forearm vasodilatator effect of intra‐arterial ANP infusion in patients with heart failure and normal subjects and demonstrated a marked attenuation of this effect in patients with heart failure compared with normal subjects. These results are consistent with the results of a preliminary report on a study of patients and animals with heart failure that suggest that vascular responses to ANP are blunted in heart failure 24,25 . However, the mechanism of this attenuation of the ANP‐induced vasodilatator effect in heart failure is unknown.…”

“…These results are consistent with the results of a preliminary report on a study of patients and animals with heart failure that suggest that vascular responses to ANP are blunted in heart failure. 24,25 However, the mechanism of this attenuation of the ANP-induced vasodilatator effect in heart failure is unknown. The present study suggests one possibility, namely that the attenuated vasodilatator effect of ANP in patients with heart failure may be attributable to impaired endothelial function found in heart failure, because previous investigators have shown that agonist-induced NO-mediated vasodilatation in response to muscarinic stimulation is impaired in the peripheral circulation of patients with heart failure.…”

Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics

“…Moreover, natriuretic peptide signaling gains greater prominence in heart failure as plasma natriuretic peptide concentrations become markedly elevated (Burnett, Jr. et al, 1986; Sugawara et al, 1988; Tikkanen et al, 1985). Vasodilatory and diuretic responses to ANP are blunted in heart failure animal models (Drexler et al, 1987; Riegger et al, 1988) and in heart failure patients (Cody et al, 1986; Hirooka et al, 1990; Tsutamoto et al, 1993). The blunted response has been attributed by some to a reduction in NPR-A expression, as seen in the pulmonary vasculature of heart failure patients (Tsutamoto et al, 1992) and in the systemic vasculature of rats models of high-output heart failure (Garcia et al, 1992).…”

Decreased responsiveness of vascular postjunctional α1‐, α2‐adrenoceptors and neuropeptide Y1 receptors in rats with heart failure

“…1994a). As a result of increased sympathetic outflow, systemic vacular resistance is increased (Drexler et al . 1987) and may contribute to the high mortality in this heart failure rat model (Pfeffer et al .…”