Biomedical subjects

Simon C Malpas

Publications and source records attributed to Simon C Malpas.

24 records · Page 2Linked to original sources

PubMed2002

Is the chronically denervated kidney supersensitive to catecholamines?

One method for discerning the role of the renal sympathetic nerves in the regulation of renal function has been to chronically denervate one kidney. One concern with this approach is that increased renal responsiveness to plasma levels of norepinephrine may develop over time. This may reduce the apparent magnitude of the effect of the renal nerves or indeed completely mask their effect. In the present experiment, we used the rabbit unilateral denervated kidney model to examine the acute renal blood flow responses to phenylephrine to determine if there were differences between the responses in chronically denervated kidneys compared with either intact or acutely denervated kidneys. In addition, we examined the responses in rabbits that had been made hypertensive using a continuous infusion of ANG II for 7 wk. We found that chronic denervation did not result in increased renal responsiveness to phenylephrine compared with either the intact or acutely denervated kidney, suggesting that differences in renal function between renal nerve-intact and -denervated kidneys observed in previous studies are unlikely to be confounded by supersensitivity. These results suggest that the unilateral denervated kidney model is a valid model to study the role of the renal nerves in the regulation of renal function.

Angiotensin II↗

PubMed2002

Dynamic baroreflex control of blood pressure: influence of the heart vs. peripheral resistance.

The aim in the present experiments was to assess the dynamic baroreflex control of blood pressure, to develop an accurate mathematical model that represented this relationship, and to assess the role of dynamic changes in heart rate and stroke volume in giving rise to components of this response. Patterned electrical stimulation [pseudo-random binary sequence (PRBS)] was applied to the aortic depressor nerve (ADN) to produce changes in blood pressure under open-loop conditions in anesthetized rabbits. The stimulus provided constant power over the frequency range 0-0.5 Hz and revealed that the composite systems represented by the central nervous system, sympathetic activity, and vascular resistance responded as a second-order low-pass filter (corner frequency approximately 0.047 Hz) with a time delay (1.01 s). The gain between ADN and mean arterial pressure was reasonably constant before the corner frequency and then decreased with increasing frequency of stimulus. Although the heart rate was altered in response to the PRBS stimuli, we found that removal of the heart's ability to contribute to blood pressure variability by vagotomy and beta(1)-receptor blockade did not significantly alter the frequency response. We conclude that the contribution of the heart to the dynamic regulation of blood pressure is negligible in the rabbit. The consequences of this finding are examined with respect to low-frequency oscillations in blood pressure.

Animals↗

PubMedDate not supplied

Effect of renal perfusion pressure on responses of intrarenal blood flow to renal nerve stimulation in rabbits.

1. We investigated how sympathetic nerve activity and renal perfusion pressure (RPP) interact in controlling renal haemodynamics in pentobarbitone-anaesthetized rabbits. 2. Renal blood flow (RBF) was reduced by electrical renal nerve stimulation (0.5-8 Hz), with RPP set using an extracorporeal circuit to 65, 100 and 135 mmHg. 3. Responses of RBF and cortical laser Doppler flux to renal nerve stimulation were blunted by increased RPP. For example, 4 Hz stimulation reduced RBF by 68 +/- 7% with baseline perfusion pressure approximately 65 mmHg, but only by 22 +/- 3% at approximately 135 mmHg. Medullary laser Doppler flux was less responsive than cortical laser Doppler flux to renal nerve stimulation and its response was not dependent on perfusion pressure. 4. When perfusion pressure was clamped at its baseline level during renal nerve stimulation, responses of RBF and cortical laser Doppler flux, but not medullary laser Doppler flux, were still blunted with increased baseline perfusion pressure. 5. A frequency rich stimulus was applied to assess the effects of perfusion pressure on dynamic neural control of RBF. Renal blood flow responded similarly at each level of perfusion pressure, as a low-pass filter with a pure time delay. 6. Our results suggest that, in the rabbit extracorporeal circuit model, increased RPP blunts the ability of steady state renal nerve stimulation to reduce cortical, but not medullary perfusion. However, in this model the level of RPP appears to have little impact on dynamic neural control of RBF.

Animals↗

PubMedDate not supplied

Neural control of renal medullary perfusion.

There is strong evidence that the renal medullary circulation plays a key role in long-term blood pressure control. This, and evidence implicating sympathetic overactivity in development of hypertension, provides the need for understanding how sympathetic nerves affect medullary blood flow (MBF). The precise vascular elements that regulate MBF under physiological conditions are unknown, but likely include the outer medullary portions of descending vasa recta and afferent and efferent arterioles of juxtamedullary glomeruli, all of which receive dense sympathetic innervation. Many early studies of the impact of sympathetic drive on MBF were flawed, both because of the methods used for measuring MBF and because single and often intense neural stimuli were tested. Recent studies have established that MBF is less sensitive than cortical blood flow (CBF) to electrical renal nerve stimulation, particularly at low stimulus intensities. Indeed, MBF appears to be refractory to increases in endogenous renal sympathetic nerve activity within the physiological range in all but the most extreme cases. Multiple mechanisms appear to operate in concert to blunt the impact of sympathetic drive on MBF, including counter-regulatory roles of nitric oxide and perhaps even paradoxical angiotensin II-induced vasodilatation. Regional differences in the geometry of glomerular arterioles are also likely to predispose MBF to be less sensitive than CBF to any given vasoconstrictor stimulus. Failure of these mechanisms would promote reductions in MBF in response to physiological activation of the renal nerves, which could, in turn, lead to salt and water retention and hypertension.

Animals↗

PubMedDate not supplied

Long-term recording of sympathetic nerve activity: the new frontier in understanding the development of hypertension?

1. With increasing evidence that the sympathetic nervous system plays a critical role in the development of hypertension, focus is turning to how these signals translate to a chronic increase in arterial pressure. 2. The kidney's role in the control of salt and water homeostasis makes it an obvious target for such investigations. However, to date, many studies have been restricted to experiments lasting only a few hours or, at most, a few days, whereas others may use indirect methods of assessing sympathetic activity rather than direct recordings. 3. We review current approaches used to determine the effects of renal sympathetic nerve activity (SNA) on arterial pressure and suggest possible avenues of future investigation. We propose that although afferent inputs, such as from chemoreceptors and baroreceptors, are important for the short-term control of blood pressure via regulation of SNA to multiple organs, it is highly likely that alternative signals are important for setting the long-term level of renal SNA. 4. Emerging evidence indicates circulating angiotensin II is hormone that may act on the central nervous system to regulate renal SNA, renal function and, thus, blood pressure. 5. We propose that an integral part of future studies seeking an understanding of the genesis of hypertension should include chronic direct recordings of renal SNA.

Adrenergic Fibers↗

PubMedDate not supplied

Nitric oxide and sympathetic nerve activity in the control of blood pressure.

1. Endothelial dysfunction marked by impairment in the release of nitric oxide (NO) is seen very early in the development of hypertension and is considered important in mediating the impaired vascular tone evident in essential hypertensive patients. 2. Recently, a hypothesis has emerged that NO acting as a neurotransmitter in the brain can modulate levels of sympathetic nerve activity and thereby blood pressure. The NO inhibition model of hypertension has been used to explore the possibility that a decrease in levels of NO can cause an increase in levels of sympathetic nerve activity that can mediate the hypertension. 3. In the present review, we examine the literature regarding the role of NO in setting the mean level of sympathetic nerve activity and blood pressure. Although the acute effects of NO inhibition are well understood, the chronic interaction between the sympathetic nervous system and NO has only been investigated using indirect measures of sympathetic nerve activity, such as ganglionic blockade. This has led to inconsistent results regarding the role of NO in modulating sympathetic nerve activity chronically. 4. Some of the conflicting results may be explained by differences in the 'background' levels of angiotensin (Ang) II. Evidence suggests that NO may interact with AngII and baroreceptor afferent inputs in the central nervous system to set the mean level of sympathetic nerve activity. 5. We suggest chronic NO inhibition can increase sympathetic nerve activity if baroreceptor input is intact and AngII levels are elevated. Although studies exploring the actions of NO or AngII in isolation are useful for gathering initial information, future studies should focus on their interactions and their role in setting the long-term levels of sympathetic activity and blood pressure.

Adrenergic Fibers↗