Pressure-response characteristics of arterial baroreceptors (BR) were shown recently to be reset following a 15- to 20-min change in mean arterial pressure (MAP); the curves shifted in the direction of the MAP change. To characterize this rapid BR resetting process more precisely than in vitro studies allow, we utilized an in vitro aortic arch-aortic nerve preparation from Wistar-Kyoto rats. Pressure ramps were used to determine the discharge response curves of single BRs following exposure to precisely controlled conditioning pressures. Rapid resetting occurred in all BRs and followed an exponential time course with a 3- to 5-min time constant. The reset curves were stable for 1 h and were completely reversible. The curves were shifted along the pressure axis in a parallel manner, i.e., pressure threshold (Pth) changed but slope and mean asymptotic discharge were unaltered. In experiments lasting as long as 7 h in which more than two MAP steps were possible, in vitro rapid resetting was a very consistent and reproducible process. Quantitatively, the extent of resetting (delta Pth/delta MAP) averaged 0.33 over an MAP range of 40-160 mmHg. In vitro resetting therefore appears very similar to that observed in vivo, suggesting that the conditioning pressure is the primary, perhaps the sole, determinant of resetting. Resetting occurred at subthreshold MAPs, demonstrating action potentials are not a prerequisite. Efferent neural or hormonal influences are also not required.

Children raised with extended exposure to environmental tobacco smoke (ETS) experience increased cough and wheeze. This study was designed to determine whether extended ETS exposure enhances citric acid-induced cough and bronchoconstriction in young guinea pigs via a neurokinin-1 (NK-1) receptor mechanism at the first central synapse of lung afferent neurons, the nucleus tractus solitarius. Guinea pigs were exposed to ETS from 1 to 6 weeks of age. At 5 weeks of age, guide cannulae were implanted bilaterally in the medial nucleus tractus solitarius at a site that produced apnea in response to the glutamate agonist D,L-homocysteic acid. At 6 weeks of age, either vehicle or a NK-1 receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius of the conscious guinea pigs who were then exposed to citric acid aerosol. ETS exposure significantly enhanced citric acid-induced cough by 56% and maximal Penh (a measure of airway obstruction) by 43%, effects that were attenuated by the NK-1 receptor antagonist in the nucleus tractus solitarius. We conclude that in young guinea pigs extended exposure to ETS increases citric acid-induced cough and bronchoconstriction in part by an NK-1 receptor mechanism in the nucleus tractus solitarius.

The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously with aortic pressure and diameter. At constant suprathreshold pressure, NE had two dose-dependent effects. Inhibition was produced at low concentrations (10(-10)-10(-7) M), whereas excitation was produced at high concentrations (10(-6)-10(-5) M). Inhibition was attributed to BR unloading since the response was consistent with the fall in diameter, was mimicked by angiotensin II (10(-10)-10(-6) M), and was prevented by pretreatment with the smooth muscle relaxant sodium nitroprusside (10(-6) M) or the selective alpha 1-adrenergic antagonist, prazosin (10(-6) M). Excitation was attributed to direct activation of the BR endings since this response was independent of changes in diameter, was not mimicked by angiotensin II, and was not prevented by sodium nitroprusside but was blocked by prazosin. These results indicate that NE has two modes of action, one mediated by contraction of local vascular smooth muscle and the other due to direct excitation of the nerve endings. It was also found that BR discharge at given diameters decreased more when pressure was lowered (smooth muscle passive) than when the aorta constricted (smooth muscle active). Furthermore, if diameter was held constant during smooth muscle contraction, discharge increased, as opposed to decreasing at constant pressure. These later results suggest that BR responses to vasoactive agents reflect not only changes in wall dimension but perhaps changes in wall tension and/or the coupling relation between BR and smooth muscle structures.

In an earlier study, we examined the pressure-response characteristics of rat aortic baroreceptors with C-fibre (non-medullated) afferents. Compared with aortic baroreceptor fibres with A-fibre (medullated) afferents, the C-fibres were activated at higher pressures and discharged more irregularly when stimulated with a steady level of pressure. Here we examine the relationship between discharge and the aortic diameter in these two types of afferents in rats and rabbits. An in vitro aortic arch/aortic nerve preparation was used to record single-fibre activity simultaneously with aortic arch pressure and diameter. Diameter was measured using a highly sensitive non-contact photoelectric device. Baroreceptor discharge was characterized by stimulating the nerve endings with either slow pressure ramps from subthreshold to 200-250 mmHg, at a rate of rise of 2 mmHg s-1, or pressure steps from subthreshold to suprathreshold levels, at amplitudes of 110-180 mmHg. In response to these inputs, C-fibres in rabbits (conduction velocities= 0.8-2.2 m s-1) behaved much like those in rats. The C-fibres had significantly higher pressure thresholds (95 +/- 3 mmHg vs. 53 +/- 2 mmHg; mean +/- SEM), lower threshold frequencies (2.4 +/- 0.5 vs. 27.7 +/- 1.8 spikes s-1), lower maximum discharge frequencies (22.7 +/- 2.3 vs. 65 +/- 5.8 spikes s-1) and more irregular discharge in response to a pressure step when compared with A-fibres (conduction velocities of 8-16 m s-1). When plotted against diameter, C-fibre ramp-evoked discharge increased gradually at first, and then rose steeply at increasingly higher ramp pressures where aortic diameter became relatively constant. In contrast, A-fibre discharge was linearly related to diameter over a wide range of pressure. These results suggest two interpretations: (1) The relation between stretch and C-fibre discharge is highly non-linear, with a marked increase in sensitivity at large diameters. (2) C-fibres are stimulated by changes in intramural stress rather than stretch.

In hypertensive subjects, a single bout of dynamic exercise results in an immediate lowering of blood pressure back toward normal. This postexercise hypotension (PEH) also occurs in the spontaneously hypertensive rat (SHR). In both humans and SHRs, PEH features a decrease in sympathetic nerve discharge, suggesting the involvement of central nervous system pathways. Given that substance P is released in the nucleus tractus solitarius (NTS) by activation of baroreceptor and skeletal muscle afferent fibers during muscle contraction, we hypothesized that substance P acting at neurokinin-1 (NK-1) receptors in the NTS might contribute to PEH. We tested the hypothesis by determining, in conscious SHRs, whether NTS microinjections of the NK-1 receptor antagonist SR-140333 before exercise attenuated PEH. The antagonist, in a dose (60 pmol) that blocked substance P- and spared D,L-homocysteic acid-induced depressor responses, significantly attenuated the PEH by 37%, whereas it had no effect on blood pressure during exercise. Vehicle microinjection had no effect. The antagonist also had no effect on heart rate responses during both exercise and the PEH period. The data suggest that a substance P (NK-1) receptor mechanism in the NTS contributes to PEH.