Dynamic interactions between arterial pressure and sympathetic nerve activity: role of arterial baroreceptors

The role of arterial baroreceptors in controlling arterial pressure (AP) variability through changes in sympathetic nerve activity was examined in conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured continuously during 1-h periods in freely behaving rats that had been subjected to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before study (n = 10 in each group). Fast Fourier transform analysis revealed that chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing the so-called Mayer waves, and induced an eightfold increase in MAP power without altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of rats, coherence between RSNA and MAP was maximal in the MF band and was usually weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP showed the characteristics of a second-order low-pass filter containing a fixed time delay ( approximately 0.5 s). These results indicate that arterial baroreceptors are not involved in production of respiratory-related oscillations of RSNA but play a major role in the genesis of synchronous oscillations of MAP and RSNA at the frequency of Mayer waves. The weak coupling between slow fluctuations of RSNA and MAP in sham-operated and SAD rats points to the interference of noise sources unrelated to RSNA affecting MAP and of noise sources unrelated to MAP affecting RSNA.     

Forebrain mechanisms in neurogenic hypertension

In recent years a considerable amount of experimental evidence has suggested that forebrain structures are involved in the pathogenesis of high arterial pressure (AP). However, little is known about the location and function of these supramedullary structures in the hypertensive process. This report reviews a series of studies done to identify the location and to determine the contribution of some forebrain structures to both the development and maintenance of the elevated AP following selective aortic baroreceptor deafferentation (ABD). In the first series of studies, it was demonstrated that the elevated AP resulting from ABD was associated with increased metabolic activity in several forebrain structures: the paraventricular nucleus of the hypothalamus (PVH), supraoptic nucleus, nucleus circularis, median preoptic nucleus, subfornical organ (SFO), and central nucleus of the amygdala. In the second series, bilateral electrolytic lesions of the PVH were shown to prevent the development of and (or) reverse the elevated AP after ABD. Similarly, bilateral microinjections of the neurotoxin kainic acid into the PVH were shown to reverse the increased AP after ABD. In the final series, electrolytic lesions of the SFO were shown to attenuate the rise in AP after ABD and (or) to reduce the elevated AP to a level that remained above control values. Taken together, these data suggest that the PVH and SFO are components of a neuronal circuit involved in the hypertensive process following ABD, and that the SFO likely exerts its effect through the PVH.     

Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation

Matsumoto, Koichiro, Hisamichi Aizawa, Hiromasa Inoue,Mutsumi Shigyo, Shohei Takata, and Nobuyuki Hara. Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation. J. Appl.Physiol. 81(6): 2358-2364, 1996.We investigatedthe role of neurogenic inflammation and the subsequent mechanisms incigarette smoke-induced airway hyperresponsiveness in guinea pigs.Exposure to cigarette smoke was carried out at tidal volume for 3 min.Airway responsiveness to histamine was determined before and aftersmoke exposure followed by bronchoalveolar lavage (BAL). Plasmaextravasation was evaluated by measuring the extravasation of Evansblue dye in the airway. Cigarette smoke produced significant airwayhyperresponsiveness and plasma extravasation, with an influx ofneutrophils in BAL fluid. FK-224 (10 mg/kg iv), a tachykinin antagonistat NK₁ andNK₂ receptors, significantly inhibited these changes. The thromboxane (Tx)B₂ concentration was increased inBAL fluid after smoke exposure and was significantly inhibited byFK-224. OKY-046 (10 mg/kg iv), a Tx synthase inhibitor, significantlyinhibited airway hyperresponsiveness but had no effect on neutrophilinflux or plasma extravasation. The results suggest that neurogenicinflammation and the subsequent generation of Tx in the airway areimportant in the development of the airway hyperresponsiveness inducedby cigarette smoke.

     

Humoral and neurogenic factors in two-kidney renovascular hypertension

A "bolus" dose (110 microgram) of the angiotesin II (A II)-blocker 1-Sar-8-Ala-A II (Saralasin, S) followed by its slow rate infusion (5 microgram/min/rat) for thirty min, was injected before and after the complete ganglionic blockade by pentolinium (P) in unanaesthetized unilaterally clipped renal hypertensive rats (the opposite kidney remained untouched). Pentolinium was also injected like a "bolus" dose (3 mg) followed by slow infusion (0.1 mg/min/rat) for thirty min. The observations were made until the fifth week after clipping the left renal artery. A consistent maximal hypotensive response was observed after the "bolus test" with both drugs. When S was the first drug injected, an inverse correlation was found between the percent decrease in arterial pressure (BP) by S and the percent decrease in BP by P (r = --0.83, P < 0.01, n = 8). Thus whenever a greater hypotensive effect was obtained by S, a smaller neural pressor component remained to be blocked by P. On the other hand, when P was the first drug injected a lesser A II pressor component remained to be blocked by S in the hypertensive rats. The results suggest that a considerable A II pressor effect in two-kidney renovascular hypertension is mediated via neurogenic mechanisms from the first week. A direct pressor vasoconstriction was found to be significant in cases with very high plasma-renin activity.     

Arterial baroreceptors mediate the inhibitory effect of acute increases in arterial blood pressure on thirst

The present study sought to determine whether arterial baroreceptor afferents mediate the inhibitory effect of an acute increase in arterial blood pressure (AP) on thirst stimulated by systemically administered ANG II or by hyperosmolality. Approximately 2 wk after sinoaortic denervation, one of four doses of ANG II (10, 40, 100, or 250 ng. kg(-1) x min(-1)) was infused intravenously in control and complete sinoaortic-denervated (SAD) rats. Complete SAD rats ingested more water than control rats when infused with 40, 100, or 250 ng x kg(-1) x min(-1) ANG II. Furthermore, complete SAD rats displayed significantly shorter latencies to drink compared with control rats. In a separate group of rats, drinking behavior was stimulated by increases in plasma osmolality, and mean AP was raised by an infusion of phenylephrine (PE). The infusion of PE significantly reduced water intake and lengthened the latencies to drink in control rats but not in complete SAD rats. In all experiments, drinking behavior of rats that were subjected to sinoaortic denervation surgery but had residual baroreceptor reflex function (partial SAD rats) was similar to that of control rats. Thus it appears that arterial baroreceptor afferents mediate the inhibitory effect of an acute increase in AP on thirst stimulated by ANG II or hyperosmolality.     

Glutamate release in midbrain periaqueductal gray by activation of skeletal muscle receptors and arterial baroreceptors

We have previously reported that both skeletal muscle receptor and arterial baroreceptor afferent inputs activate neurons in the dorsolateral (DL) and lateral regions of the midbrain periaqueductal gray (PAG). In this study, we determined whether the excitatory amino acid glutamate (Glu) is released to mediate the increased activity in these regions. Static contraction of the triceps surae muscle for 4 min was evoked by electrical stimulation of the L7 and S1 ventral roots in cats. Activation of arterial baroreceptor was induced by intravenous injection of phenylephrine. The endogenous release of Glu from the PAG was recovered with the use of a microdialysis probe. Glu concentration was measured by the HPLC method. Muscle contraction increased mean arterial pressure (MAP) from 98 +/- 10 to 149 +/- 12 mmHg (P < 0.05) and increased Glu release in the DL and lateral regions of the middle PAG from 0.39 +/- 0.10 to 0.73 +/- 0.12 microM (87%, P < 0.05) in intact cats. After sinoaortic denervation and vagotomy were performed, contraction increased MAP from 95 +/- 12 to 158 +/- 15 mmHg, and Glu from 0.34 +/- 0.08 to 0.54 +/- 0.10 microM (59%, P < 0.05). The increases in arterial pressure and Glu were abolished by muscle paralysis. Phenylephrine increased MAP from 100 +/- 13 to 162 +/- 22 mmHg and increased Glu from 0.36 +/- 0.10 to 0.59 +/- 0.18 microM (64%, P < 0.05) in intact animals. Denervation abolished this Glu increase. Summation of the changes in Glu evoked by muscle receptor and arterial baroreceptor afferent inputs was greater than the increase in Glu produced when both reflexes were activated simultaneously in intact state (123% vs. 87%). These data demonstrate that activation of skeletal muscle receptors evokes release of Glu in the DL and lateral regions of the middle PAG, and convergence of afferent inputs from muscle receptors and arterial baroreceptors in these regions inhibits the release of Glu. These results suggest that the PAG is a neural integrating site for the interaction between the exercise pressor reflex and the arterial baroreceptor reflex.