Acute Changes In Arterial Pressure Research Articles

The interplay between sympathetic overactivity, hypertension and heart rate variability (review, invited).

The control of arterial pressure is a complex interaction of the long- and short-term influences of hormones, local vascular factors, and neural mechanisms. The autonomic nervous system and its sympathetic arm play important roles in the regulation of blood pressure, and overactivity of sympathetic nerves may have an important role in the development of hypertension and related cardiovascular disorders. The baroreceptor system opposes either increases or decreases in arterial pressure, and the primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The ability of the baroreflex to powerfully buffer acute changes in arterial pressure is well established, but the role of the arterial baroreceptor reflex in long-term control of arterial pressure has been a topic of many debate and controversy for decades. The sympathetic nervous system and arterial baroreceptor reflex control of renal sympathetic nerve activity has been proposed to play a role in long-term control of arterial pressure. The aim of this paper has been to review the postulated role of sympathetic activation.

Hemodynamic sensing using subcutaneous photoplethysmography

Pacemakers and implantable defibrillators presently operate without access to hemodynamic information. If available, such data would allow tailoring of delivered therapy according to perfusion status, optimization of device function, and enhancement of disease monitoring and management. A candidate method for hemodynamic sensing in these devices is photoplethysmography (PPG), which uses light to noninvasively detect changes in blood volume. The present study tested the hypotheses that PPG can function in a subcutaneous location, that the acute changes in blood volume it detects are directly proportional to changes in arterial pressure, and that optimum pacing intervals identified by it are concordant with those determined by arterial pressure. Aortic pressure and PPG were simultaneously recorded in 10 dogs under general anesthesia during changes in atrioventricular (AV) delay and bursts of rapid pacing to simulate tachyarrhythmias. Direct proportionality between transient changes in pressure and PPG waveforms was tested using regression analysis. Scatter plots had a linear appearance, with correlation coefficients of 0.95 (SD 0.03) and 0.72 (SD 0.24) for rapid-pacing and AV delay protocols, respectively. The data were well described by a directly proportional relationship. Optimum AV delays estimated from the induced changes in aortic pressure and PPG waveforms were concordant. This preliminary canine study demonstrates that PPG can function subcutaneously and that it may serve as a surrogate for acute changes in arterial pressure.

Impairment of sympathetic baroreceptor reflexes in obese Zucker rats

Adult obese Zucker rats (OZRs) have elevated sympathetic vasomotor tone and arterial pressure (AP) with blunted baroreflex-mediated changes in heart rate (HR) compared with adult lean Zucker rats (LZRs). The present study examined whether compromised cardiac baroreflexes are indicative of attenuated sympathetic responses. In addition, because juvenile OZRs have a normal mean AP, we determined whether baroreflexes are fully functional prior to hypertension. At 13 wk, adult OZRs had an elevated baseline mean AP compared with LZRs (137 +/- 3 vs. 123 +/- 5 mmHg, P < 0.05) under urethane anesthesia. Phenylephrine-induced increases in AP evoked smaller inhibitions of splanchnic sympathetic nerve activity (SNA) and HR in OZRs compared with LZRs. In addition, sympathoexcitatory responses to nitroprusside-induced hypotension were also blunted in OZRs. Sigmoid analysis revealed a decreased gain, a higher mean AP at the midpoint of the curve (AP(50)), and a reduced range of changes in SNA in OZRs. In contrast, at 7 wk of age, although juvenile OZRs weighed more than LZRs (313 +/- 13 vs. 204 +/- 4 g, P < 0.05), mean AP was comparable in both groups (122 +/- 5 vs. 121 +/- 4 mmHg, not significant). In these rats, rapid changes in AP evoked comparable changes in SNA and HR in OZRs and LZRs. Sigmoid analysis revealed that, although the gain of the reflex was blunted in OZRs (P < 0.05), the mean AP(50) and range of changes in SNA were comparable in OZRs and LZRs. Together, these data indicate that in adult OZRs, sympathetic responses to acute changes in AP are smaller than those observed in adult LZRs and that impairment of baroreceptor reflexes in OZR is not limited to the regulation of HR but extends to sympathetic vasomotor control. In addition, most of these deficits in baroreflex control of SNA develop in adulthood long after the onset of obesity and when other deficits in cardiovascular regulation are present.

Nitric oxide in the control of renal hemodynamics and excretory function

Experimental evidence has now been amassed to indicate that inhibition of nitric oxide (NO) synthase reduces total or regional renal blood flow by approximately 25 to 30% and markedly increases the renal vascular resistance, demonstrating that basal release of NO helps to maintain the relatively low vascular resistance that is characteristic for the kidney. It has been demonstrated that intraarterial administration of NO synthase inhibitors causes marked reductions in sodium excretion without changes in filtered load and suppressed the arterial pressure-induced natriuretic responses in the kidney. We also demonstrated that a constant rate infusion of a NO donor in dogs pretreated with a NOS inhibitor resulted in increases in sodium excretion but failed to restore the slope of the relation between arterial pressure and sodium excretion, suggesting that an alteration in intrarenal NO production rate during changes in arterial pressure is involved in the mediation of pressure natriuresis. Further experiments in dogs performed in our laboratory have confirmed that there is a direct relationship between changes in arterial pressure and intrarenal NO activity measured using NO-sensitive microelectrodes in the renal tissue. These arterial pressure-induced changes in intrarenal NO activity were seen positively correlated with the changes in urinary excretion rates of sodium. Collectively, these data suggest that acute changes in arterial pressure alter intrarenal NO production, which inhibits tubular sodium reabsorption to manifest the phenomenon of pressure natriuresis.

Detection of apical Na(+)/H(+) exchanger activity inhibition in proximal tubules induced by acute hypertension.

We previously showed that acute arterial hypertension induces an inhibition of fluid and NaCl reabsorption in proximal tubules of Sprague-Dawley rats, which is associated with a rapid reversible internalization of apical Na(+)/H(+) exchanger in brush border. To determine whether there is a corresponding inhibition of apical Na(+)/H(+) exchanger activity in proximal tubules to account for the reduced tubular reabsorption, an instrument capable of measuring intracellular pH (pH(i)) ratiometrically and repeatedly on the surface of kidney with high temporal resolution is required. We report the design and validation of such a fluorimetric system based on two ultraviolet nitrogen-pulsed lasers and a photomultiplier. pH(i) of proximal tubules in situ was measured with pH-sensitive fluorescence dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein at 5 Hz. Using the initial rate of change of pH(i) (dpH(i)/dt) during luminal Na(+) removal as an index of apical Na(+)/H(+) exchanger activity, the exchanger activity was found to be reduced by 52 +/- 11% (n = 14, P < 0.05) compared with the baseline after 20 min of induced acute hypertension. The inhibition of Na(+)/H(+) exchange activity was alleviated when the blood pressure was returned to prehypertensive level. These observations indicate that acute changes in arterial pressure can reversibly inhibit apical Na(+)/H(+) exchanger activity, which might contribute to pressure natriuresis in proximal tubule.

Responses to acute changes in arterial pressure on renal medullary nitric oxide activity in dogs.

A direct relationship between renal arterial pressure (RAP) and cortical tissue nitric oxide (NO) activity in the canine kidney was reported earlier. We have conducted further experiments to evaluate medullary NO responses to alterations in RAP with the use of a NO-selective microelectrode inserted into the renal medulla of 6 anesthetized, sodium-replete dogs. Graded reductions in RAP (from 140 to 80 mm Hg) elicited decreases in medullary tissue NO concentration, with a slope of 10.2+/-4.5 nmol x L(-1) x mm Hg(-1). These changes in NO levels were associated with decreases in urinary excretion rate of nitrate and nitrite (U(NOx)V; control value, 1.7+/-0.03 nmol x min(-1) x g(-1); slope, 0.02+/-0.004 nmol x min(-1) x g(-1) x mm Hg(-1)) and sodium excretion (U(Na)V; control, 3.2+/-0.7 micromol x min(-1) x g(-1); slope, 0.06+/-0.02 micromol x min(-1) x g(-1) x mm Hg(-1)) without changes in glomerular filtration rate control (0.84+/-0.06 mL x min(-1) x g(-1)). Intra-arterial administration of the NO synthase inhibitor N(omega)-nitro-L-arginine (NLA; 50 microg x kg(-1) x min(-1)) decreased medullary NO concentration by 218+/-55 nmol x L(-1) (n=5) and attenuated the relationship between RAP and NO concentration (slope, 2.7+/-2.2 nmol x L(-1) x mm Hg(-1)). NLA infusion decreased U(NOx)V (0.8+/-0.06 nmol x min(-1) x g(-1)) and U(Na)V (1.1+/-0.2 micromol x min(-1) x g(-1)) without changes in glomerular filtration rate and attenuated RAP versus U(Nox)V and U(Na)V relationships. Total and regional blood flows, as measured by electromagnetic and laser Doppler needle flow probes, respectively, remained autoregulated both before and during NLA infusion. These data support the hypothesis that acute changes in RAP elicit changes in intrarenal NO production, which may participate in the mediation of pressure natriuresis.

NITRIC OXIDE IN THE MEDIATION OF PRESSURE NATRIURESIS

1. Recent studies have indicated that nitric oxide (NO) production in the kidney contributes to the regulation of renal haemodynamics and excretory function. Inhibition of nitric oxide synthase (NOS) reduces renal blood flow by approximately 25% and markedly reduces sodium excretion without reductions in filtered load. In particular, inhibition of NO synthesis markedly suppresses the slope of the arterial pressure-mediated response in sodium excretion. 2. Further studies have shown that constant intrarenal infusion of a NO donor in dogs treated with a NOS inhibitor produced diuretic and natriuretic responses but failed to restore the slope of the pressure-induced natriuretic response. These data indicate that an alteration in intrarenal NO activity, rather than the simple presence of NO during changes in arterial pressure is required for full expression of pressure natriuretic responses. 3. In support of the hypothesis that NO is involved in the mediation of pressure natriuresis, we also recently demonstrated a direct relationship between changes in arterial pressure and urinary excretion rate of sodium as well as nitrate and nitrite (a marker for endogenous NO activity) in the presence of efficient autoregulation of cortical and medullary blood flow. 4. The direct inhibitory actions of NO on tubular sodium reabsorption have also been observed in cultured tubular cells as well as isolated, perfused cortical collecting duct segments. 5. Thus, the collective data suggest that acute changes in arterial pressure induce changes in intrarenal NO production, which may directly alter tubular reabsorptive function to manifest the phenomenon of pressure natriuresis.

Autonomic responses of the insular cortex in hypertensive and normotensive rats

Lesion and focal cerebral ischemia of the insular cortex (IC) results in elevated renal sympathetic nerve activity (RSNA) and arterial pressure (AP) in the Wistar rat, while the opposite effect is observed in the spontaneously hypertensive rat (SHR). Acute changes in AP, heart rate (HR) and RSNA were measured in propofol-anesthetized and conscious SHR (n = 17) and Wistar rats (n = 17) during pressure injection of D,L-homocysteic acid (DLH; 100 mM) and lidocaine (LID; 20 mg/ml) into the IC. DLH injections (200 nl) into the IC of anesthetized Wistar rats resulted in a significant increase in MAP (mean change = +27 +/- 7 mmHg; P < 0.05) and a significant decrease in HR (-22 +/- 9 beats/min) and RSNA (-11 +/- 4 microV.s). Neither DLH nor LID injections into the IC of anesthetized SHR affected MAP or RNA. DLH and LID injections (500 nl) into the IC of conscious Wistar rats both resulted in a significant increase in MAP (+26 +/- 5 mmHg; 11 +/- 4 mmHg, respectively). Neither DLH nor LID injections had any cardiovascular effects in the conscious SHR. It therefore appears that the IC of conscious Wistar rats has a tonic inhibitory output, while neural excitation is capable of eliciting pressor responses. Conversely, the IC of SHR appears to exert no tonic influence on MAP.

Dynamic, short-term coupling between changes in arterial pressure and urine flow.

Pressure diuresis refers to the direct effect of arterial pressure (AP) on the rate of urine flow (UF). On the basis of computer modeling, pressure diuresis has been viewed as a long-term mechanism that acts to set the level of the blood volume and, thus, the steady-state AP. There are no systematic studies, however, on the rapidity with which changes in AP induce changes in UF in vivo. Therefore, we measured the delay between induced changes in AP and the subsequent change in UF. Nine anesthetized rats were instrumented with arterial, venous, and ureteral catheters. AP and UF were measured every 2 s, while acute changes in AP were induced by 1) occlusion of the aorta above or below the renal vessels; 2) brief tail pinch; or 3) intravenous administration of acetylcholine (1 microgram), phenylephrine (1 microgram), or angiotensin II (0.1 microgram). The rapidity of the urinary response to induced changes in AP was determined by calculating the delay between a significant change in AP (+/- 2 SD from baseline) and a significant change in UF. The delay averaged 6.0 +/- 0.5 s for all conditions. Also, examining the relationship between the magnitude of the induced changes in AP and the magnitude of the responses in UF revealed an exponential influence of AP on UF. That is, there were proportionately larger changes in UF compared with AP (< or = 10 times greater magnitude) in response to the experimental interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid baroreceptor resetting in chronic hypertension. Implications for normalization of arterial pressure.

The purpose of this study was to examine the ability of baroreceptors of renal hypertensive rabbits to reset rapidly during acute changes in arterial pressure. The carotid sinus (CS) was vascularly isolated and baroreceptor activity was recorded during slow ramp increases in CS pressure in hypertensive (one-kidney, one wrap; 127 +/- 3 mm Hg) and normotensive (one-kidney, no wrap; 85 +/- 3 mm Hg) rabbits anesthetized with chloralose. Control measurements were made after holding pressure for 10-15 minutes at the level of arterial pressure recorded before each experiment. Baroreceptor threshold pressure (Pth) was higher in hypertensives (78 +/- 4 mm Hg) compared with normotensives (55 +/- 3 mm Hg, p less than 0.05), and nerve activity was less in hypertensives over a wide range of pressure. CS distensibility (sonomicrometers) was not significantly different in the two groups. After increasing holding pressure from control by 30 and 60 mm Hg for 10-15 minutes, the extent of baroreceptor resetting (delta Pth/delta holding pressure x 100%) in normotensives was 39 +/- 6% and 33 +/- 2%, respectively, but only 14 +/- 5% and 9 +/- 3% in hypertensives (p less than 0.05). After decreasing holding pressure by 30 and 60 mm Hg, resetting was similar in normotensives (32 +/- 6% and 28 +/- 3%) and hypertensives (34 +/- 3% and 30 +/- 4%). In hypertensive rabbits, acute (10-15 minutes) exposure of baroreceptors to normotension (71 +/- 4 mm Hg) decreased Pth to 62 +/- 4 mm Hg and increased nerve activity to levels not significantly different from those of normotensive animals without altering CS distensibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of carotid sinus baroreceptor reflex on responses to phenylephrine and nitroprusside in anesthetized cats.

This study attempted to measure the extent to which the carotid sinus baroreceptor reflex attenuates the acute changes in arterial pressure during infusions of phenylephrine and nitroprusside, and to express these effects as equations which could be used in a simple computer model of the circulation. Arterial pressure and cardiac output were measured in vagotomized cats anesthetized with chloralose or pentobarbital. The carotid arteries were perfused to allow sinus pressure either to follow changes in systemic arterial pressure or to be held at the preinfusion control level, thereby eliminating the effects of the reflex. There was a linear relationship between arterial pressure in the presence and absence of the reflex, and the changes in arterial pressure were attenuated to one-third by the reflex while cardiac output was not significantly changed. These effects are described by simple equations involving peripheral resistance, heart rate, and venous compliance. The activity of the reflex was not significantly different in cats anesthetized with pentobarbital or chloralose, and our data do not support the view that these anesthetic agents depress the vasomotor component of the carotid sinus reflex.

RELATIVE ROLES OF THE SYMPATHETIC AND PARASYMPATHETIC NERVOUS SYSTEMS IN THE REFLEX CONTROL OF HEART RATE.

This study was designed to define the relative roles of the sympathetic and parasympathetic nervous systems in the reflex alterations of heart rate consequent to changes in arterial pressure. In 23 experiments carried out on 22 anesthetized dogs and in studies performed on four trained, unanesthetized dogs, acute changes in arterial pressure were produced by administering drugs acting on the peripheral vascular bed. The effects of acutely elevating systemic pressure were also investigated in four intact unanesthetized human subjects. Augmenting arterial pressure above control levels with graded doses of phenylephrine always slowed heart rate strikingly. Although complete sympathetic blockade with guanethidine or pronethalol did not significantly alter the degree of slowing, parasympathetic blockade with atropine or vagotomy essentially abolished this response. Conversely, lowering pressure with intravenous injections of nitroglycerin always raised heart rate in the control state, a response abolished by sympathetic blockade with guanethidine or nethalide, but not by parasympathetic blockade with vagotomy or atropine. Thus, when arterial pressure rises above control, the decrease in heart rate is mediated by the parasympathetic nervous system, withdrawal of sympathetic activity playing no detectable role; when pressure falls below control levels, the elevation of heart rate is mediated primarily by the sympathetic nervous system. These findings are not consonant with the traditional concept of control of heart rate which predicates simultaneous reciprocal changes in activity occurring in the two components of the autonomic nervous system.