Many studies have shown that atrial natriuretic peptide (ANP) reduces mean arterial pressure (MAP) in conscious animals by lowering cardiac output (CO) with no change or even increased total peripheral resistance (TPR). Because ANP is thought to be a vasodilator, the lack of fall in TPR in conscious animals is generally considered to be due to autonomic reflex increases in vascular resistance. In the present study in conscious, trained, chronically instrumented dogs (n = 7), we measured hemodynamic and renal excretory responses to 30-min infusions of alpha-human ANP (alpha hANP; 25, 50, and 100 ng.kg-1.min-1) in the presence and absence of autonomic nervous system blockade using the ganglion blocking agent pentolinium. In the absence of blockade, MAP and CO fell, whereas TPR rose with alpha hANP infusions, but these changes did not reach significance. There were significant increases in renal vascular resistance (RVR; 16-25%) and mesenteric vascular resistance (MVR; 14-40%). During autonomic nervous system blockade, alpha hANP caused dose-related reductions in MAP (7-12%), due to falls in CO (13-34%). Remarkably, the absence of autonomic reflex responses exposed substantial dose-related increases in TPR (5-33%). Autonomic blockade did not alter the ANP-induced increases in MVR but did abolish the rises in RVR. In summary, ANP caused vasoconstriction in mesenteric vasculature and substantial vasoconstriction in other nonrenal areas, independent of autonomic reflexes.