Dependence of renal blood flow on renal artery stenosis measured using CT angiography.

PURPOSE: The present study investigates the suitability of computed tomography angiography (CTA) depicting the degree of renal artery stenosis for estimating renal blood flow (RBF) in a kidney. MATERIALS AND METHODS: We investigated renal artery stenosis assessment by CTA in eight adult female hybrid pigs with an ultrasound probe implanted at the renal vein for RBF measurement. An inflatable metal-free cuff was placed around the renal artery to control the RBF. The RBF was then reduced in four steps. For each reduced RBF value and baseline RBF, CTA with a reconstructed slice thickness of 0.625 mm was performed in the arterial phase following injection of 80 ml of nonionic intravenous contrast medium. The radius of the stenotic and non-stenotic renal artery segment was measured in the reconstructed images. RESULTS: A significant linear correlation (p < 0.0001) was found between the relative apparent stenosis (calculated as the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment) and RBF. The linear regression yielded a slope of 0.57 and a y-axis of 24.1 %. A significant linear correlation (p < 0.0001) was also found between the relative true stenosis (the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment at baseline) and the RBF. The linear regression yielded a slope of 0.67 and a y-axis of 13.8 %. CONCLUSION: The results show that the relative stenosis apparent on CTA differs from the true degree of renal artery stenosis. Nevertheless, the degree of renal artery stenosis determined by CTA provides a reliable estimate of the resulting RBF reduction.

Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat).

Renal volume regulation is modulated by the action of cyclooxygenases (COX) and the resulting generation of prostanoids. Epithelial expression of COX isoforms in the cortex directs COX-1 to the distal convolutions and cortical collecting duct, and COX-2 to the thick ascending limb. Partly colocalized are prostaglandin E synthase (PGES), the downstream enzyme for renal prostaglandin E(2) (PGE(2)) generation, and the EP receptors type 1 and 3. COX-1 and related components were studied in two kidney-one clip (2K1C) Goldblatt hypertensive rats with combined chronic ANG II or bradykinin B(2) receptor blockade using candesartan (cand) or the B(2) antagonist Hoechst 140 (Hoe). Rats (untreated sham, 2K1C, sham + cand, 2K1C + cand, sham + Hoe, 2K1C + Hoe) were treated to map expression of parameters controlling PGE(2) synthesis. In 2K1C, cortical COX isoforms did not change uniformly. COX-2 changed in parallel with NO synthase 1 (NOS1) expression with a raise in the clipped, but a decrease in the nonclipped side. By contrast, COX-1 and PGES were uniformly downregulated in both kidneys, along with reduced urinary PGE(2) levels, and showed no clear relations with the NO status. ANG II receptor blockade confirmed negative regulation of COX-2 by ANG II but blunted the decrease in COX-1 selectively in nonclipped kidneys. B(2) receptor blockade reduced COX-2 induction in 2K1C but had no clear effect on COX-1. We suggest that in 2K1C, COX-1 and PGES expression may fail to oppose the effects of renovascular hypertension through reduced prostaglandin signaling in late distal tubule and cortical collecting duct.

Nitric oxide and the role of blood pressure variability to the kidney.

Blood pressure variability is buffered by at least two mechanisms: the arterial baroreceptor reflex and nitric oxide (NO). Only recently is the importance of blood pressure variations on cardiovascular control being investigated. Here we report of a study performed in conscious dogs, in which renovascular hypertension was induced. Reduction of renal arterial pressure (RAP) to 85 mmHg for 24 h elicited profound hypertension by 60 mmHg (vs. control: 110 +/- 3 mmHg; P < 0.01). This was accompanied by reduced volume and sodium excretion (-48% of control, P < 0.01 and -80% of control, P < 0.01, respectively) and augmented renin release by more than two-fold (P < 0.01). This intervention was compared with a protocol in which RAP was reduced to the same mean value, however, RAP oscillated by +/-10 mmHg at 0.1 Hz. This manoeuvre led to a transient increase in NO3 excretion in urine (P < 0.01), blunted antidiuresis (-14% of control) as well as antinatriuresis (-40% of control) and attenuated the increased renin release by 30% (P < 0.05). In consequence, the magnitude of blood pressure increase was only half as high as that observed during static reduction of RAP (P < 0.01). It is concluded that blood pressure oscillations to the kidney have a profound influence on water and electrolyte balance and on renin release, which alleviates the onset of Goldblatt hypertension.

Renal arterial pressure variability. A role in blood pressure control?

It is becoming generally appreciated that blood pressure (BP) fluctuations can have major pathophysiological importance in hypertensives. Nonetheless, little is known regarding the influence of short-term changes in BP on kidney function, a crucial control element for long-term BP regulation. This overview summarizes first efforts to unravel the importance of BP dynamics on renal function. It seems that the kidney is not only an important control element in the BP regulation network; the renal vascular bed may also be very susceptible to BP oscillations, which can occur, for example, from baroreflex malfunction.

Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats.

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.

Blood pressure control in eNOS knock-out mice: comparison with other species under NO blockade.

Changes in arterial blood pressure (ABP) lead to changes in vascular shear stress. This mechanical stimulus increases cytosolic Ca2+ in endothelial cells, which in turn activates the endothelial isoform of the nitric oxide synthase. The subsequently formed NO reaches the adjacent vascular smooth muscle cells, where it reduces vascular resistance in order to maintain ABP at its initial level. Thus, NO may play an important role as a physiological blood pressure buffer. Previous data on the importance of eNOS for blood pressure control are reviewed with special emphasis on the fact that endogenous nitric oxide can buffer blood pressure variability (BPV) in dogs, rats and mice. In previous studies where all isoforms of the nitric oxide synthase were blocked pharmacologically, increases in blood pressure and variability were observed. Thus, we set out to clarify which isoform of the nitric oxide synthase is responsible for this BPV controlling effect. Hence, blood pressure control was studied in knock-out mice lacking specifically the gene for endothelial nitric oxide synthase with their respective wild-type controls. One day after surgery, under resting conditions, blood pressure was increased by 47 mmHg (P < 0.05), heart rate was lower (-77 beats min-1, P < 0.05), and BPV doubled (P < 0.05). Based on these results, we conclude that chronic blood pressure levels are influenced by eNOS and that there is a blood pressure buffering effect of endogenous nitric oxide which is mediated by the endothelial isoform of the nitric oxide synthase.

Antihypertensive effect of 0.1-Hz blood pressure oscillations to the kidney.

BACKGROUND: Physiological blood pressure (BP) fluctuations with frequencies >0.1 Hz can override renal blood flow autoregulation. The influence of such immediate changes in renal perfusion pressure (RPP) on daily BP regulation, eg, via shear stress-stimulated liberation of renal endothelial NO, however, is unknown. Thus, we studied the effects of such RPP oscillations on renal function and on systemic BP during the onset of renal hypertension. METHODS AND RESULTS: Seven beagles (randomly assigned to each of the following protocols) were chronically instrumented for the measurement of systemic BP, RPP, and renal excretory function. An inflatable cuff was used to reduce and to oscillate RPP over 24 hours in the freely moving dog. Reducing RPP to 87+/-2 mm Hg diminished excretion of sodium and water and doubled plasma renin activity (PRA, n=7, P<0. 01) but had no significant effect on urinary nitrate excretion (n=6), a marker of NO generation. Superimposing 0.1-Hz oscillations (+/-10 mm Hg) onto the reduced RPP blunted hypertension, returned fluid excretion almost to control levels, and doubled renal sodium elimination. Nitrate excretion peaked at 8 hours, only to return to control values shortly thereafter. PRA, conversely, was significantly reduced during the last third of the experimental protocols. CONCLUSIONS: BP fluctuations transiently stimulate NO liberation and induce a reduction in PRA, which enhances 24-hour sodium and water excretion and markedly attenuates the acute development of renovascular hypertension.

Pressure-dependent renin release: effects of sodium intake and changes of total body sodium.

The impact of sodium intake and changes in total body sodium (TBS) for the setting of pressure-dependent renin release (PDRR) was studied in freely moving dogs. An aortic cuff allowed servo control of renal perfusion pressure (RPP) at preset values. Protocols were 1) high sodium intake (HSI), 2) low sodium intake (LSI), 3) TBS moderately increased (+3.1 mmol Na/kg body wt) by 20% reduction of RPP for 2-4 days, 4) large increase of TBS (+8.2) by combining protocol 3 with aldosterone infusion, and 5) TBS reduced (-3.1) by peritoneal dialyses. Twenty-four-hour time courses of arterial plasma renin activity (PRA) revealed that LSI increased PRA for the first 10 h only; afterward PRA did not differ between LSI and HSI. Reduced TBS increased PRA constantly, and the large increase of TBS constantly reduced PRA. PDRR stimulus-response curves (assessed 20 h after last sodium intake) revealed an exponential relationship in each protocol. PDRR was not changed by different sodium intake. Conversely, reduced TBS increased PDRR markedly, whereas the large increase of TBS suppressed it. Thus an inverse relationship between TBS and PRA, i.e., a TBS-dependent renin release, was found. This relationship was enhanced by decreasing RPP. This interplay between TBS-dependent renin release and PDRR allows the organism a differentiated reaction to changes in TBS and arterial pressure.

Blood pressure variability and urine flow in the conscious dog.

Pressure-dependent urine production is considered to be a major factor in long-term blood pressure control. The phenomenon has been well characterized for fixed levels of renal perfusion pressure (RPP), but the influence of physiological fluctuations in RPP and spontaneous variations in renal blood flow (RBF) on short-term urine flow (UV) remain unclear. To clarify this issue, we studied the interdependence of RPP, RBF, and UV in 13 conscious foxhounds during a single-step pressure reduction, under normal conditions, and with induced pressure changes. Reducing RPP in a single step to approximately 80 mmHg revealed short response times of RBF (0.4 +/- 0.1 s, n = 7) as well as of UV (8.1 +/- 0.8 s, n = 7). Under control conditions, UV was coupled with spontaneous variations of RBF (r = 0.94, P < 0.001), in contrast to RPP, which showed no significant correlation with UV (r = 0.09, P = NS). To discern the pressure and blood flow dependency of UV at a reduced RPP, we induced 0.9-mHz blood pressure oscillations (80 +/- 10 mmHg), which phase shifted RPP and RBF. Conversely, under these conditions, UV was dependent on RPP (r = 0.95, P < 0.001). These results suggest that spontaneous fluctuations in RBF around a normal baseline level lead to concomitant changes in urine production, in contrast to physiological short-term oscillations in RPP, which are not correlated to changes in UV. However, during induced oscillations of perfusion pressure, the blood flow dependence was no longer observed and UV was entirely pressure dependent.

Kinins modulate the sodium-dependent autoregulation of renal medullary blood flow.

OBJECTIVE: In the recent past it has become clear that the kallikrein-kinin system is closely intertwined with long-term blood pressure regulation. It was shown that a kinin B2 receptor blockade leads to a sodium-dependent rise in blood pressure. The underlying mechanisms of this phenomenon, however, remain unclear. The osmotic gradient of the renal medulla is a prerequisite for the preservation of volume and sodium by the kidney. We thus hypothesized, that a kinin dependent modulation of medullary blood flow accounts for the influence of sodium on blood pressure. METHODS: In 39 urethane anaesthetized rats pressure dependent regulation of whole kidney blood flow and cortical and medullary blood flow were estimated via laser-Doppler flux by a stepwise reduction of renal perfusion pressure to 30 mm Hg. RESULTS: In controls (n = 15), a reduction in renal perfusion pressure to 30 mm Hg lead to a concomitant reduction in whole kidney blood flow (25 +/- 3% of baseline) and cortical laser-Doppler flux (36 +/- 5% of baseline). In contrast, medullary laser-Doppler flux decreased only to 79 +/- 8% of the baseline level. Providing a 2% sodium chloride solution as drinking water over 5 days (n = 12), resulted in a significantly lower capability to autoregulate medullary flow (50 +/- 6% of baseline, P < 0.05). Acute subcutaneous administration of Hoe 140, a bradykinin B2 receptor antagonist (300 micrograms/kg bwt), restored autoregulation of medullary flow to almost normal levels (93 +/- 12% of baseline, P < 0.01 versus high sodium diet alone, n = 12). CONCLUSIONS: Our results indicate that B2 receptor blockade restores the attenuated autoregulation of medullary Doppler flux during sodium enriched diet. This, suggests that the kinin dependent impact of sodium on blood pressure regulation is mediated by modulations of medullary blood flow autoregulation.

Flow versus pressure in the control of renin release in conscious dogs.

In Goldblatt hypertension, renal artery stenosis reduces renal arterial pressure (RAP) and renal blood flow (RBF) and thereby increases plasma renin activity (PRA) levels. Although it is clear that reduction in RAP stimulates renin, the decrease in RBF may contribute to higher PRA as well. However, it has hitherto never been possible to dissociate a decrease in RBF from a concomitant decrease in RAP. To overcome this restriction, we used two protocols. 1) RAP was reduced in a single step to 70 +/- 0.2 mmHg (N = 8). RBF followed the sudden fall in RAP within 15 s but subsequently took on initial levels. In contrast, renal venous PRA increased from 0.95 +/- 0.22 to 5.6 +/- 1.4 ng angiotensin I.ml-1.h-1 (P < 0.05) and remained at higher values even after RBF had regained control conditions. 2) Resonance between RAP and RBF was induced by superimposing slow sinusoidal RAP waves with a period length of 450 s (N = 9), leading to a phase shift of roughly 180 degrees (time delay, 241 +/- 12 s), i.e., RBF was maximal at minimal RAP. Under these conditions, renin release was only dependent on decrements in RAP (delay of only 27 +/- 8 s). In conclusion, RBF played no major role in renin release.

Very low frequency oscillations in arterial blood pressure after autonomic blockade in conscious dogs.

The aim of this study was to investigate spontaneous variability of arterial blood pressure in conscious foxhounds in the absence of direct sympathetic and parasympathetic influences. Autonomic blockade was achieved by administration of the ganglionic blocking agent hexamethonium (n = 7). In contrast to the control group (n = 7), marked oscillations with a cycle length of 100 s (0.01 Hz) were observed. The relationship of the power densities of the oscillation band (0.01 +/- 0.005 Hz) to the total power increased threefold (0.213 +/- 0.007 vs. 0.057 +/- 0.005; P < 0.01). The 0.01-Hz oscillations typically commenced after some delay. To test whether the absence of the mechanoreceptor afferents was responsible for these fluctuations, we investigated an additional group of foxhounds that were subjected to total baroreceptor and cardiopulmonary receptor denervation (n = 7). Neither in this protocol, nor in a group subjected to denervation and ganglionic blockade (n = 6), did we observe sustained oscillations in this frequency range. Since the oscillations were not seen after combined afferent (mechanoreceptor denervation) and efferent (ganglionic) blockade, central oscillators as a source of the oscillations can be ruled out. A simple model of a circulating pressoric factor may explain the fluctuations, provided that there is a time delay between the stimulus and the release or action of the factor. The findings suggest that a circulating factor accounts for the 0.01-Hz oscillations, which is dependent on intact pathways from the cardiac receptors or baroreceptors to the central nervous system. This hypothesis is put forward since cardiopulmonary and baroreceptor denervation blocked the oscillations seen after ganglionic blockade.

Endogenous nitric oxide buffers blood pressure variability between 0.2 and 0.6 Hz in the conscious rat.

Shear stress is a potent stimulus for the formation and release of nitric oxide (NO). It seems, therefore, possible that a short-term increase in arterial blood pressure (ABP), which leads to a concomitant rise in endothelial shear stress, enhances NO release. The latter elicits a relaxation of vascular smooth muscle cells that, in turn, counteracts the initial rise in blood pressure (BP). Thus this chain of events may constitute a negative feedback loop reducing BP variability (BPV). To test this hypothesis, BP-time series were determined via telemetry in freely moving conscious Sprague-Dawley rats. Because it was reported recently that NO effects on ABP are more pronounced in females, the experiments were performed on 2 groups consisting of 10 female and 11 male animals. This was done under control conditions and after fixing NO plasma levels via an intravenous bolus of 15 mg/kg body wt N(G)-nitro-L-arginine methyl ester together with a continuous infusion of nitroprusside (15 +/- 0.8 microg/min). This combined infusion maintained mean ABP and heart rate at physiological levels, thus avoiding as much as possible interferences with other reflexes, e.g., the baroreflex. To quantitate BPV, fast Fourier transforms of the BP-time series were determined. The absolute power in the frequency range below 1 Hz increased during fixed NO to approximately 350% vs. control animals (female control, 2.1 x 10(9) +/- 1.5 x 10(8) mmHg2 vs. fixed NO, 8.0 x 10(9) +/- 1.3 x 10(9) mmHg2, P < 0.005; male control, 3.4 x 10(9) +/- 4.6 x 10(8) mmHg2 vs. fixed NO, 8.3 x 10(9) +/- 2.0 x 10(9) mmHg2, P < 0.05). This was mainly caused by a substantial rise in the power ranging from 0.2 to 0.6 Hz, which increased roughly fourfold in both females and males. It is concluded that the NO system is a potent buffer of spontaneous BP oscillations in the freely moving rat. This system is most efficient in buffering frequencies within the range of 0.2-0.6 Hz and shows no gender-specific differences with respect to its BP buffering capacity.

Chaos in blood pressure control.

A number of control mechanisms are comprised within blood pressure regulation, ranging from events on the cellular level up to circulating hormones. Despite their vast number, blood pressure fluctuations occur preferably within a certain range (under physiological conditions). A specific class of dynamic systems has been extensively studied over the past several years: nonlinear coupled systems, which often reveal a characteristic form of motion termed "chaos". The system is restricted to a certain range in phase space, but the motion is never periodic. The attractor the system moves on has a non-integer dimension. What all chaotic systems have in common is their sensitive dependence on initial conditions. The question arises as to whether blood pressure regulation can be explained by such models. Many efforts have been made to characterise heart rate variability and EEG dynamics by parameters of chaos theory (e.g., fractal dimensions and Lyapunov exponents). These method were successfully applied to dynamics observed in single organs, but very few studies have dealt with blood pressure dynamics. This mini-review first gives an overview on the history of blood pressure dynamics and the methods suitable to characterise the dynamics by means of tools derived from the field of nonlinear dynamics. Then applications to systemic blood pressure are discussed. After a short survey on heart rate variability, which is indirectly reflected in blood pressure variability, some dynamic aspects of resistance vessels are given. Intriguingly, systemic blood pressure reveals a change in fractal dimensions and Lyapunov exponents, when the major short-term control mechanism--the arterial baroreflex--is disrupted. Indeed it seems that cardiovascular time series can be described by tools from nonlinear dynamics [66]. These methods allow a novel description of some important aspects of biological systems. Both the linear and the nonlinear tools complement each other and can be useful in characterising the stability and complexity of blood pressure control.

Blood-pressure variability is buffered by nitric oxide.

The baroreflex constitutes the only hitherto known buffer of rapid blood pressure oscillations. In order to investigate the influence of nitric oxide (NO) and the sinoaortic and cardiopulmonary baroreflex pathways on the dynamic properties of blood pressure control, we determined the power spectra of 24-h blood pressure time series of conscious dogs. This was done in the intact state (n = 6), during blockade of NO synthesis via the false substrate NG-nitro-L-arginine ((L-NNA), 16.5 +/- 2 mg/kg body weight i.v., n = 5) and in animals devoid of baroreceptor reflexes (n = 5). After L-NNA, blood pressure (BP) increased by roughly 20 mmHg to 137 +/- 6 mmHg (P < 0.01), heart rate decreased from 97 +/- 6 to 68 +/- 3 beats/min (P < 0.01). The power of blood pressure variations within the frequency range 0.1-0.5 Hz was tripled by L-NNA (P < 0.05). By comparison total sinoaortic and cardiopulmonary denervation increased power of slower oscillations ( < 0.1 Hz) by a factor of 4.7 (P < 0.05). Thus, NO and the baroreceptor reflex both play an important role as physiological blood pressure buffers, NO for rapid (0.1-0.5 Hz) and the baroreflex for slower fluctuations ( < 0.1 Hz).

Complexity and "chaos" in blood pressure after baroreceptor denervation of conscious dogs.

To investigate how arterial baroreceptors affect the dynamic properties of short-term blood pressure control, we determined Lyapunov exponents and correlation dimensions of blood pressure. Two groups of conscious dogs were studied: a control group (n = 7) and a group subjected to total sinoaortic and cardiopulmonary baroreceptor denervation (n = 7). As a measure of variability, standard deviation was determined and power spectra were calculated. In the lower frequency range (f < 0.1 Hz) power density was inversely related to frequency in both groups, indicating "1/f noise." Estimating the correlation dimension via the Grassberger-Procaccia algorithm as a quantification of complexity revealed a decrease after baroreceptor denervation (1.74 +/- 0.2 vs. 3.05 +/- 0.23 control; P < 0.05). Determination of the largest Lyapunov exponents lambda 1, which indicates the sensitive dependence on initial conditions, a hallmark of chaos, also yielded a diminution after denervation (lambda 1 = 0.74 +/- 0.08 vs. 1.85 +/- 0.18, P < 0.01). The results were cross-checked with surrogate data statistics. The null hypothesis, that there is no nonlinear structure in arterial blood pressure time series, was rejected. This shows that after baroreceptor denervation, blood pressure control is less complex and less sensitive to initial conditions ("chaos"). In contrast, variability (standard deviation) is increased (22.2 +/- 3.1 denervation vs. 8.3 +/- 1.4 control; P < 0.05). It is concluded that under physiological conditions, arterial and cardiopulmonary baroreceptors reduce variability of blood pressure, however, at the cost of blood pressure being less predictable. Thus the regulation is more sensitive depending on initial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency domain of renal autoregulation in the conscious dog.

The dynamic range in which renal blood flow (RBF) autoregulation occurs was determined in eight conscious foxhounds chronically catheterized in the abdominal aorta and implanted with a transit-time flow probe over the renal artery. Sinusoidal driving pressures (amplitude of 10 mmHg) were forced on the renal arterial pressure at different frequencies by a servo-control device, and transfer functions were calculated. Only one frequency range was found below which the gain of the transfer function declined and in which the phase angle increased (n = 8). This indicates the presence of a potent mechanism for renal autoregulation in the examined frequency range between 0.0031 and 0.08 Hz, which buffers changes in blood flow < 0.02 Hz. After furosemide treatment, one indicator for autoregulation (phase shift of transfer function) was significantly blunted at low frequencies (n = 6). Furosemide, however, did not reduce the phase shift to zero, suggesting that some autoregulation still remained in the frequency range between 0.04 and 0.08 Hz. In conclusion, autoregulation of RBF during sinusoidal changes in driving pressure between 0.0031 and 0.02 Hz is mediated by a single mechanism, which can be blocked by the acute administration of furosemide. The residual phase shift between arterial pressure and RBF in the transfer function observed during sinusoidal changes in driving pressure between 0.04 and 0.08 Hz suggests the presence of a second mechanism for RBF autoregulation.

Does low frequency power of arterial blood pressure reflect sympathetic tone?

We tested whether power spectral analysis of arterial blood pressure (ABP) is a feasible tool to detect differences in peripheral sympathetic nerve activity in normotensive and hypertensive rats with differing basal sympathetic tones. Nine Wistar Kyoto rats (WKY), 10 Sprague-Dawley rats (SD), 10 spontaneously hypertensive rats (SHR) and 9 hypertensive transgenic rats harbouring the mouse Ren-2 gene (TGR) were chronically instrumented with femoral artery catheters and nerve electrodes around the sympathetic major splanchnic nerve. Two days after surgery ABP and splanchnic nerve activity (SpNA) were recorded in the conscious state during basal conditions as well as during alpha 1-adrenergic receptor blockade. Power spectra and squared coherence in the low (LF, 0.02-0.20 Hz), mid (MF, 0.20-0.80 Hz) and high (HF, respiration peak +/- 0.3 Hz) frequency bands were calculated for ABP and SpNA. Mean blood pressure in SHR (133 +/- 8 mmHg) and TGR (142 +/- 8 mmHg) was significantly higher (P < 0.05) than in WKY (115 +/- 3 mmHg) and SD (95 +/- 4 mmHg). SpNA in SHR was higher than in WKY (23.4 +/- 6.4 microV vs. 11.6 +/- 0.8 microV, P < 0.05) while SpNA in TGR was lower than in SD (20.1 +/- 3.9 microV vs. 28.8 +/- 4.2 microV, P < 0.05). LF and MF components of ABP variability were not significantly higher in those rats with high sympathetic tones. However, alpha 1-adrenergic receptor blockade reduced LF and MF components of ABP and SpNA in all strains except SHR. LF and MF coherence was not greater in rats with high sympathetic tones than in those with low sympathetic tones. The reduction of LF and MF components of ABP variability by alpha 1-adrenergic receptor blockade indicates an important contribution of peripheral sympathetic nerve activity to LF and MF blood pressure variability on an acute basis. However, the lack of higher LF and MF power in the ABP spectra of those rats with high SpNA together with the finding that LF and MF coherence was not higher in those rats with high SpNA led to the conclusion that LF and MF spectral components of ABP do not appear to be suitable markers for the prevailing sympathetic nerve activity.

The blood pressure buffering capacity of nitric oxide by comparison to the baroreceptor reflex.

To compare the contribution of nitric oxide (NO) to the buffering of short-term and circadian fluctuations of arterial blood pressure with that of the baroreceptor reflex, conscious foxhounds were subjected to continuous 24-h blood pressure recordings. A pressure transducer was placed into the lumen of the abdominal aorta. Telemetry recordings were done under control conditions, following blockade of NO formation by intravenous bolus injection of NG-nitro-L-arginine (L-NNA; 16.5 +/- 2 mg/kg body wt) and after total sinoaortic and cardiopulmonary denervation in five dogs each. L-NNA produced a sustained elevation of mean arterial pressure (MAP; 137.2 +/- 6.4 mmHg vs. control, 112.9 +/- 3.7 mmHg). After denervation, no significant increase of MAP was found (113.5 +/- 4.1 mmHg), but the standard deviation of the MAP histogram was significantly greater (22.5 +/- 3.1 vs. 10.6 +/- 0.9 mmHg, P < 0.05). Sequential spectral analysis showed that total power between 0 and 0.5 Hz was elevated more than twofold after L-NNA (P < 0.05). This was due primarily to increased power in the range above 0.1 Hz. After denervation, total power increased about three-fold (P < 0.05), almost exclusively occurring below 0.04 Hz. Power in the range above 0.2 Hz was diminished, although not significantly. It is concluded that in the conscious dog, NO, as well as the baroreceptor reflex, is an effective blood pressure buffer. NO is most effective above 0.1 Hz, whereas the baroreceptors primarily buffer fluctuations slower than 0.04 Hz.