Nonuniform enhancement of baroreflex sensitivity by atrial natriuretic peptide in conscious rats and dogs

Abstract

The influence of atrial natriuretic peptide (ANP) on the blood pressure (BP)-heart rate (HR) baroreflex was studied in conscious chronically instrumented dogs and rats. In both species, sigmoid steady-state baroreflex curves were constructed from the baroreflex changes in HR to alternating slow injections of vasopressor and vasodepressor drugs. When this method was used in dogs, ANP caused a small but significant (P < 0.05) enhancement of the sensitivity (22 +/- 10%) and curvature (26 +/- 10%) of the baroreflex, which was without a change in HR range. In rats, ANP had no significant effect on any baroreflex parameter derived from steady-state curves. By contrast, in the same rats, fast reflex HR responses to rapid increases in BP (ramp) exposed a substantial (81 +/- 21%) ANP-induced enhancement of baroreflex sensitivity. Contribution from arterial vs. nonarterial afferents to the baroreflex is not uniform between these two techniques (steady state reflects largely arterial baroreceptor input, ramp evokes a greater proportion of cardiopulmonary afferent activation). The present study demonstrated that baroreceptor HR reflex responses to ANP depend on the baroreflex techniques employed and probably exposed a selectivity by ANP for nonarterial baroreflex pathways.

Restorative Effect of Atrial Natriuretic Peptide or Chronic Neutral Endopeptidase Inhibition on Blunted Cardiopulmonary Vagal Reflexes in Aged Rats

“…Mean ramp gain in 6-month-old rats was Ϫ2.12Ϯ0.21 beats/min per mm Hg (Figure 2A), similar to previous measurements in 3-month-old animals, 12,18 whereas in 24-monthold rats, it was Ϫ1.30Ϯ0.22 beats/min per mm Hg ( Figure 2B, PϽ0.05), representing a 39% decline with age.…”

“…In 6-month-old rats, ANP infusion significantly (PϽ0.05) increased ramp baroreflex gain to Ϫ3.20Ϯ0.24 beats/min per mm Hg ( Figure 2C; a 51% increase) in line with findings on 3-month-old rats. 12,18 In old rats, ANP also significantly (PϽ0.05) enhanced the ramp baroreflex to Ϫ2.47Ϯ0.31 beats/min per mm Hg ( Figure 2D, a 91% increase). For further details, see Figure S3B.…”

“…11,12,18,19 Briefly, (1) ramp baroreflex responses were assessed after rapid MAP increases of approximately 50 mm Hg evoked by methoxamine (100 g/kg intravenously; Sigma Chemical) aiming for a similar rate of MAP rise across all animals (approximately 20 mm Hg/s). Linear regression analysis was applied to the progressive HR responses to MAP changes.…”

ANP and Bradycardic Reflexes in Hypertensive Rats

“…The steady-state method involved alternate intravenous injections of 1 to 50 L of methoxamine hydrochloride (2 to 100 g/kg doses; Wellcome Research Laboratories) and sodium nitroprusside (1 to 50 g/kg doses; Nipride, Roche Products) to produce a series of stepped increases and decreases in mean BP (from Ϯ2 to 60 mm Hg) in each rat. 8,9,18 The steady-state changes in mean BP and HR, measured over 10 to 15 seconds, were fitted to a sigmoid logistic equation by a computer that applied the algorithm of Marquardt 18 as follows: HRϭP1ϩP2/[1ϩe P3(MAPϪP4) ], where P1 is the lower HR plateau, P2 is the HR range, P3 is the normalized gain, P4 is the arterial pressure at the midpoint of the HR range, and MAP is mean arterial pressure. The average gain (G) or slope of the curve between the 2 inflection points is given as GϭϪP2ϫP3/4.56.…”

“…2,4 -7 Studies in our laboratory have provided evidence that ANP acts preferentially on nonarterial or cardiopulmonary afferent pathways, leading to cardiac slowing. 8,9 In conscious, instrumented normotensive rats, we observed that intravenously administered ANP enhanced reflex bradycardia when a rapid "ramp" rise in blood pressure (BP) was elicited with a vasoconstrictor agent 8,9 and when chemosensitive receptors were activated by serotonin (von Bezold-Jarisch reflex) in the heart. 9 We interpreted these findings to indicate a selective effect of ANP on cardiac vagal afferents of both mechanosensory and chemosensory pathways, since the "ramp" method invokes predominantly nonarterial baroreceptor input, 10 and the von Bezold-Jarisch reflex activates cardiac chemosensitive receptors on vagal afferents.…”