An atrial natriuretic factor analogue at low doses attenuates forearm reflex vasoconstriction to cardiopulmonary receptor deactivation in patients with hypertension.
Contrasting data exist about a possible modulation of the autonomic function by atrial natriuretic factor (ANF) in human beings, particularly at low, biologically, significant concentrations. We have evaluated that possibility by increasing plasma ANF levels through the infusion of a synthetic analogue (WY-47,663, anaritide) in five male patients with mild to moderate uncomplicated hypertension. Nonhypotensive lower body negative pressure (-10 mm Hg x 5 min) was used to selectively deactivate cardiopulmonary receptors and to stimulate sympathetic efferent tone reflexogenically. ANF was given at either a low rate (0.005 micrograms/kg/min x 60 min, which was previously shown to increase plasma ANF in a range compatible with physiologic stimuli) or at a high rate (0.05 micrograms/kg/min x 60 min, each). Administration of ANF was preceded and followed by vehicle infusion (Haemacell x 30 min). Forearm blood flow (venous plethysmography), intraarterial blood pressure, and heart rate were monitored continuously, and venous immunoreactive ANF, plasma renin activity, aldosterone level, and venous hematocrit were measured at the end of both control and infusion periods. Arterial norepinephrine values, an indirect index of sympathetic discharge, were measured at rest and during lower body negative pressure conditions. Graded systemic ANF infusion increased immunoreactive ANF and venous hematocrit, decreased aldosterone level and plasma renin activity, whereas resting norepinephrine levels, blood pressure, and heart rate did not change. Lower body negative pressure decreased forearm blood flow during vehicle infusion, but it lost its vasoconstrictor effect during infusion of ANF. To identify the site of that inhibitory action, ANF was also infused into the brachial artery at rates that raised local but not systemic levels of immunoreactive ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
Pedrinelli
R
R
Hypertension Unit, I Clinica Medica, University of Pisa, Italy.
Taddei
S
S
Favilla
S
S
Simonini
N
N
Spessot
M
M
Panarace
G
G
Salvetti
A
A
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008150:Lower Body Negative Pressure; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011311:Pressoreceptors / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D004232:Diuretics; D010446:Peptide Fragments; C042703:anaritide; D009320:Atrial Natriuretic Factor