Role of neuropeptide Y in renal sympathetic vasoconstriction: studies in normal and congestive heart failure rats.

Sympathetic nerve activity, including that in the kidney, is increased in heart failure with increased plasma concentrations of norepinephrine and the vasoconstrictor cotransmitter neuropeptide Y (NPY). We examined the contribution of NPY to sympathetically mediated alterations in kidney function in normal and heart failure rats. Heart failure rats were created by left coronary ligation and myocardial infarction. In anesthetized normal rats, the NPY Y(1) receptor antagonist, H 409/22, at two doses, had no effect on heart rate, arterial pressure, or renal hemodynamic and excretory function. In conscious severe heart failure rats, high-dose H 409/22 decreased mean arterial pressure by 8 +/- 2 mm Hg but had no effect in normal and mild heart failure rats. During graded frequency renal sympathetic nerve stimulation (0 to 10 Hz), high-dose H 409/22 attenuated the decreases in renal blood flow only at 10 Hz (-36% +/- 5%, P <.05) in normal rats but did so at both 4 (-29% +/- 4%, P <.05) and 10 Hz (-33% +/- 5%, P <.05) in heart failure rats. The glomerular filtration rate, urinary flow rate, and sodium excretion responses to renal sympathetic nerve stimulation were not affected by high-dose H 409/22 in either normal or heart failure rats. NPY does not participate in the regulation of kidney function and arterial pressure in normal conscious or anesthetized rats. When sympathetic nervous system activity is increased, as in heart failure and intense renal sympathetic nerve stimulation, respectively, a small contribution of NPY to maintenance of arterial pressure and to sympathetic renal vasoconstrictor responses may be identified.

Validity of measures of cognitive processes and general ability for learning and performance on highly complex computerized tutors: is the g factor of intelligence even more general?

Theoretical arguments and analyses from 2 studies provide compelling evidence that computerized measures of information-processing skills and abilities are highly useful supplements to more traditional, paper-based measures of general mental ability for predicting individuals' capacity to learn from and perform on highly challenging, multifaceted tutors. These tutors were designed to emulate learning and performance in complex, real-world settings. Hierarchical confirmatory factor analysis provided evidence that a general, higher order factor model with general ability at the apex could quite adequately and singularly account for the individual-differences data, both traditional and cognitive-process measures. Results are interpreted in light of the utility and generality of human cognitive abilities.

Chaotic behavior of renal sympathetic nerve activity: effect of baroreceptor denervation and cardiac failure.

Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in conscious rats subjected to either complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation) or induction of congestive heart failure (CHF). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In control rats, this yielded a system whose correlation dimension converged to a low value over the embedding dimension range of 10-15 and whose greatest Lyapunov exponent was positive. Complete baroreceptor denervation was associated with a decrease in the correlation dimension of the system (before 2.65 +/- 0.27, after 1.64 +/- 0.17; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.201 +/- 0.008 bits/data point before, 0.177 +/- 0.004 bits/data point after, P < 0.02). CHF, a state characterized by impaired sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, was associated with a similar decrease in the correlation dimension (control 3.41 +/- 0.23, CHF 2.62 +/- 0.26; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.205 +/- 0.048 bits/data point control, 0.136 +/- 0.033 bits/data point CHF, P < 0.02). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, occurring either physiologically or pathophysiologically, is associated with a decrease in the correlation dimensions of the system and a reduction in chaotic behavior.

Functional significance of the pattern of renal sympathetic nerve activation.

To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 +/- 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses.

Effect of metoprolol administration on renal sodium handling in experimental congestive heart failure.

BACKGROUND: Long-term metoprolol therapy improves cardiac performance and decreases mortality in patients with chronic congestive heart failure (CHF). This study examined the effect of long-term metoprolol therapy on renal sodium handling in an experimental rat model of CHF. METHODS AND RESULTS: Rats with left coronary ligation and myocardial infarction-induced CHF were treated with metoprolol (1.5 mg. kg-1. h-1) or vehicle for 3 weeks by osmotic minipump. They were then evaluated for their ability to excrete a short-term sodium load (5% body weight isotonic saline infusion over 30 minutes) and a long-term sodium load (change from low- to high-sodium diet over 8 days). All CHF rats had left ventricular end-diastolic pressure >10 mm Hg, and heart weight/body weight ratios averaged 0.68+/-0.02% (versus control of approximately 0.40%). Compared with vehicle CHF rats (n=19), metoprolol CHF rats (n=18) had lower basal values of mean arterial pressure (122+/-3 versus 112+/-3 mm Hg) and heart rate (373+/-14 versus 315+/-9 bpm) and decreased heart rate responses to intravenous doses of isoproterenol. During short-term isotonic saline volume loading, metoprolol CHF rats excreted 54+/-4% more of the sodium load than vehicle CHF rats. During long-term dietary sodium loading, metoprolol CHF rats retained 28+/-3% less sodium than vehicle CHF rats. CONCLUSIONS: Metoprolol treatment of rats with CHF results in an improved ability to excrete both short- and long-term sodium loads.

Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.

To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.

Effect of endogenous angiotensin II on renal nerve activity and its cardiac baroreflex regulation.

The effects of physiologic alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity and its cardiac baroreflex regulation were studied. The effect of angiotensin II type 1 receptor blockade with intracerebroventricular losartan was examined in conscious rats consuming a low, normal, or high sodium diet that were instrumented for the simultaneous measurement of right atrial pressure and renal sympathetic nerve activity. The gain of cardiac baroreflex regulation of renal sympathetic nerve activity (% delta renal sympathetic nerve activity/mmHg mean right atrial pressure) was measured during isotonic saline volume loading. Intracerebroventricular losartan did not decrease arterial pressure but significantly decreased renal sympathetic nerve activity in low (-36+/-6%) and normal (-24+/-5%), but not in high (-2+/-3%) sodium diet rats. Compared with vehicle treatment, losartan treatment significantly increased cardiac baroreflex gain in low (-3.45+/-0.20 versus -2.89+/-0.17) and normal (-2.89+/-0.18 versus -2.54+/-0.14), but not in high (-2.27+/-0.15 versus -2.22+/-0.14) sodium diet rats. These results indicate that physiologic alterations in endogenous angiotensin II activity tonically influence basal levels of renal sympathetic nerve activity and its cardiac baroreflex regulation.

Exaggerated natriuresis as a candidate intermediate phenotype in spontaneously hypertensive rats.

OBJECTIVE: To determine whether exaggerated natriuresis and exaggerated renal sympathoinhibition during volume loading constitute an intermediate phenotype in spontaneously hypertensive rats. DESIGN: The borderline hypertensive rat, the F1 of a cross between a spontaneously hypertensive rat and a normotensive Wistar-Kyoto rat, is a NaCl-sensitive model of genetic hypertension. In addition to hypertension, borderline hypertensive rats fed 8% NaCl food develop characteristic alterations in regulation of renal sympathetic nerve activity and neural regulation of renal function similar to those in the spontaneously hypertensive rat parent. Like the Wistar-Kyoto rat parent, borderline hypertensive rats fed 1% NaCl food remain normotensive and do not exhibit these alterations in renal sympathetic neural mechanisms. These renal sympathetic neural mechanisms constitute a complex quantitative trait that could represent an intermediate phenotype. METHODS: A backcross population, developed by mating borderline hypertensive rats with Wistar-Kyoto rats, was fed 8% NaCl food for 12 weeks from age 4 to 16 weeks. Responses to intravenous isotonic saline volume loading (10% body weight/30 min) in 81 backcross rats chronically instrumented for measurement of mean arterial pressure, renal sympathetic nerve activity, and urinary sodium excretion were determined. RESULTS: Mean arterial pressure was 105-180 mmHg and was not correlated to the magnitude either of the decrease in renal sympathetic nerve activity or of the increase in urinary sodium excretion during volume loading. CONCLUSIONS: These two aspects of the complex quantitative trait, exaggerated natriuresis and exaggerated renal sympathoinhibition during volume loading, are not part of an intermediate phenotype in spontaneously hypertensive rats.

Angiotensin receptor antagonist improves cardiac reflex control of renal sodium handling in heart failure.

In rats with congestive heart failure, type 1 angiotensin II receptor antagonist treatment (losartan) decreases basal renal sympathetic nerve activity and improves arterial baroreflex regulation of renal sympathetic nerve activity. This investigation examined the effect of losartan on cardiac baroreflex regulation of renal sympathetic nerve activity and renal sodium handling in rats with congestive heart failure. Losartan treatment decreased arterial pressure from 120 +/- 3 to 93 +/- 5 mmHg and increased the afferent (from 0.95 +/- 0.21 to 2.22 +/- 0.42% delta afferent vagal nerve activity/mmHg mean right atrial pressure, P < 0.05) and overall gain (from -1.14 +/- 0.19 to -4.20 +/- 0.39% delta renal sympathetic nerve activity/mmHg mean right atrial pressure, P < 0.05) of the cardiac baroreflex. During isotonic saline volume loading, urinary sodium excretion increased from 2.4 +/- 0.8 to 10.5 +/- 1.3 mueq/min in vehicle-treated rats (excretion of 52 +/- 3% of the load) and from 3.0 +/- 1.0 to 15.1 +/- 1.8 mu eq/min in losartan-treated rats (excretion of 65 +/- 4% of the load, P < 0.05). When rats were changed from a low- to a high-sodium diet, cumulative sodium balance over 5 days was 7.8 +/- 0.6 meq in vehicle-treated rats and 4.2 +/- 0.4 meq in losartan-treated rats (P < 0.05). In congestive heart failure, losartan treatment improved cardiac baroreflex regulation of renal sympathetic nerve activity, which was associated with improved ability to excrete acute and chronic sodium loads.

Reflex effects on renal nerve activity characteristics in spontaneously hypertensive rats.

The effects of arterial and cardiac baroreflex activation on the discharge characteristics of renal sympathetic nerve activity were evaluated in conscious spontaneously hypertensive and Wistar-Kyoto rats. In spontaneously hypertensive rats compared with Wistar-Kyoto rats, (1) arterial baroreflex regulation of renal sympathetic nerve activity was reset to a higher arterial pressure and the gain was decreased and (2) cardiac baroreflex regulation of renal sympathetic nerve activity exhibited a lower gain. With the use of sympathetic peak detection analysis, the inhibition of integrated renal sympathetic nerve activity, which occurred during both increased arterial pressure (arterial baroreflex) and right atrial pressure (cardiac baroreflex), was due to parallel decreases in peak height with little change in peak frequency in both spontaneously hypertensive and Wistar-Kyoto rats. Arterial and cardiac baroreflex inhibition of renal sympathetic nerve activity in Wistar-Kyoto and spontaneously hypertensive rats is due to a parallel reduction in the number of active renal sympathetic nerve fibers.

Reflex influences on renal nerve activity characteristics in nephrosis and heart failure.

Cardiac baroreflex regulation of efferent renal sympathetic nerve activity (ERSNA) is abnormal in nephrotic syndrome (NS). The purpose of the present study was to examine the responses of amplitude and frequency of synchronized ERSNA discharge in anesthetized NS rats subjected to reflex maneuvers that alter the activity of and the interaction between aortic and cardiac baroreceptors. Steady-state ERSNA was analyzed in three groups of anesthetized rats: control, NS, and congestive heart failure (CHF) (in the latter, the defect in cardiac baroreflex regulation of ERSNA is peripheral rather than central). In protocol A, analysis was performed during control, after bilateral aortic depressor nerve section, after bilateral cervical vagus nerve section, and during central vagus nerve stimulation (VAGSTIM). In protocol B, analysis was performed during control, after bilateral cervical vagus nerve section, after bilateral aortic depressor nerve section, and during central aortic depressor nerve stimulation. In protocol A, VAGSTIM decreased ERSNA and peak height (fewer active fibers), but not peak frequency, in control and CHF but not NS rats. In NS rats, this lack of effect of VAGSTIM was specific for ERSNA, because depressor and bradycardia responses to VAGSTIM were unaffected. In protocol B, central aortic depressor nerve stimulation decreased ERSNA and peak height, but not peak frequency, in control, CHF, and NS rats similarly. It is concluded that the defect in cardiac baroreflex function in NS is specific for ERSNA, is central rather than peripheral, and affects the number of active renal sympathetic nerve fibers rather than their firing frequency.

Effect of endogenous angiotensin II on renal nerve activity and its arterial baroreflex regulation.

To determine the effects of physiological alterations in endogenous angiotensin II (ANG II) activity on basal renal sympathetic nerve activity and its arterial baroreflex regulation, the effect of ANG II receptor (AT1) blockade with losartan was examined in conscious rats consuming low, normal, or high sodium diet that were instrumented for the simultaneous measurement of arterial pressure and renal sympathetic nerve activity. Intravenous losartan decreased arterial pressure in low (-27 +/- 4 mmHg) and normal (-15 +/- 2 mmHg) but not in high sodium diet rats (-5 +/- 2 mmHg). When arterial pressure had been restored to the prelosartan value with methoxamine infusion, renal sympathetic nerve activity was decreased in low (-27 +/- 4%) and normal (-20 +/- 3%) but not in high sodium diet rats (-5 +/- 2%). Arterial baroreflex regulation of renal sympathetic nerve activity was shifted to a lower pressure (arterial pressure at midrange) in low (-8 +/- 2 mmHg) and normal (-7 +/- 2 mmHg) but not in high sodium diet rats (0 +/- 2 mmHg). Intracerebroventricular losartan did not significantly decrease arterial pressure but decreased renal sympathetic nerve activity in low (-28 +/- 5%) and normal (-20 +/- 4%) but not in high sodium diet rats (-2 +/- 2%). Arterial baroreflex regulation of renal sympathetic nerve activity was shifted to a lower pressure (arterial pressure at midrange) in low (-7 +/- 2 mmHg) and normal (-5 +/- 1 mmHg) but not in high sodium diet rats (0 +/- 2 mmHg). These results indicate that physiological alterations in endogenous ANG II activity tonically influence basal levels of renal sympathetic nerve activity and its arterial baroreflex regulation.

Differentiated sympathetic neural control of the kidney.

Anatomic and neurophysiological methods were used to identify functionally specific subgroups of renal sympathetic nerve fibers. The distribution of diameters of the predominating unmyelinated fibers showed a major mode at 1.1 microns and a minor mode at 1.6 microns. The conduction velocity was 2.10 +/- 0.10 m/s, consistent with unmyelinated C fibers. Analysis of strength-duration relationships during renal nerve stimulation showed that both rheobase and chronaxie values for renal blood flow were greater than those for urinary flow rate and were independent of stimulation frequency. This difference suggests a higher stimulation threshold (smaller diameter) for those renal nerve fibers involved in the renal blood flow response (renal vasoconstriction) compared with those for the urinary flow rate response (antidiuresis) to renal nerve stimulation. Single renal units that responded to preganglionic splanchnic nerve stimulation were studied. Those with spontaneous activity (88%) responded to stimulation of arterial baroreceptors, arterial and central chemoreceptors, and peripheral thermoreceptors, whereas those that lacked spontaneous activity (12%) responded only to stimulation of peripheral thermoreceptors (known to produce renal vasoconstriction). A minority population of single renal units has been identified that, although renal vasoconstrictor, does not exhibit other characteristic features of vasoconstrictor neurons (i.e., responsiveness to stimulation of arterial baroreceptors and arterial and central chemoreceptors). These findings suggest the existence of functionally specific subgroups of renal nerve fibers.

Characteristics of renal sympathetic nerve activity in sodium-retaining disorders.

Characteristics of renal sympathetic nerve activity in conscious rats with established congestive heart failure, cirrhosis, or nephrotic syndrome were analyzed using three methods: mean integrated voltage over time, power spectrum analysis, and sympathetic peak detection analysis. Compared with control rats, all three disease models had increased mean integrated voltage. On power spectrum analysis, all three disease models had increased relative power at the heart rate frequency, indicating that it was related to renal sympathetic nerve discharge coupled to the cardiac cycle. Congestive heart failure and nephrotic syndrome rats showed increased relative power in the low-frequency range, whereas cirrhotic and nephrotic syndrome rats showed decreased relative power in the high-frequency range. On sympathetic peak detection analysis, the frequency of sympathetic peaks was greater in the three disease models compared with the control rats. In cirrhotic rats, the distribution of sympathetic peak heights was shifted toward an increased number of peaks of lesser height. It is concluded that basal renal sympathetic nerve activity is chronically increased in these disease models. This is manifest as increased power coupled to the cardiac cycle, which may reflect the disease-specific defects in arterial and cardiac baroreflex control. In cirrhosis, there is possible selective activation of a subgroup of renal sympathetic nerve fibers.

Renal sympathetic neural mechanisms as intermediate phenotype in spontaneously hypertensive rats.

The borderline hypertensive rat, the F1 of a cross between a hypertensive spontaneously hypertensive rat (SHR) and a normotensive Wistar-Kyoto (WKY) rat, is a NaCl-sensitive model of genetic hypertension. In addition to hypertension, borderline hypertensive rats fed 8% NaCl develop characteristic alterations in the regulation of efferent renal sympathetic nerve activity and the neural control of renal function that are similar to those observed in the SHR parent. Like the normotensive WKY rat parent, borderline hypertensive rats fed 1% NaCl remain normotensive and do not exhibit these alterations in renal sympathetic neural mechanisms. These renal sympathetic neural mechanisms constitute a complex quantitative trait that may represent an intermediate phenotype. They have a plausible pathogenetic role in hypertension and are different between SHR and WKY rats. This study evaluated two aspects of this complex quantitative trait, enhanced renal sympathoexcitation with air-jet stress and enhanced renal sympathoinhibition with guanabenz, as a candidate intermediate phenotype. As neither of these aspects was observed in two-kidney, one clip Goldblatt-hypertensive rats, this suggests that the trait is not secondary to hypertension from an acquired cause. In a backcross population (F1 x WKY) fed 8% NaCl for 12 weeks, both enhanced renal sympathoexcitation with air-jet stress and enhanced renal sympathoinhibition with guanabenz cosegregated with the hypertension. These results support renal sympathetic neural mechanisms as an intermediate phenotype in SHR.

Hepatorenal baroreflex in cirrhotic rats.

A hepatorenal baroreflex has been described in which increases in intrahepatic sinusoidal pressure stimulate an intrahepatic baroreceptor, resulting in increases in afferent hepatic (HNA) and efferent renal sympathetic nerve activity (RNA). Hepatic denervation prevents the increase in RNA. This baroreflex is postulated to contribute to the increase in RNA found in cirrhosis in which intrahepatic sinusoidal pressure is increased. However, the increased fibrosis in the cirrhotic liver may render the intrahepatic baroreceptor less sensitive to increases in intrahepatic sinusoidal pressure. By use of thoracic inferior vena caval constriction, intrahepatic sinusoidal pressure (i.e., inferior vena caval pressure, IVCP) was increased in control rats and rats with cirrhosis due to common bile duct ligation (CBDL) while HNA and RNA were measured. With increases in IVCP of 5 mmHg, increases in HNA (+38 +/- 2 and +44 +/- 3%) and RNA (+25 +/- 1 and +34 +/- 3%) were not different in control and CBDL rats, respectively. The slope gain, % delta HNA/delta IVCP, was +7.1 +/- 0.6 and +8.1 +/- 0.7%/mmHg in control and CBDL rats, respectively. Therefore the hepatorenal baroreflex is not desensitized in the CBDL rat, and the hepatorenal baroreflex is capable of contributing to the increase in RNA observed in cirrhosis.

Increased renal nerve activity in cardiac failure: arterial vs. cardiac baroreflex impairment.

Cardiac failure is characterized by increased renal sympathetic nerve activity that is associated with an impairment of both arterial and cardiac baroreceptor reflex function. These reflex dysfunctions are in the afferent limb at the level of the peripheral baroreceptors. This study sought to define the relative quantitative magnitude of the defects in arterial and cardiac baroreceptor function in cardiac failure. Renal sympathetic nerve activity was measured in anesthetized normal control rats and rats with cardiac failure (left coronary ligation) during sequential random order sinoaortic denervation and vagotomy to interrupt afferent input from the arterial and cardiac baroreceptors, respectively. Increases in renal sympathetic nerve activity after individual or combined sinoaortic denervation and vagotomy were less (P < 0.05 for both) in cardiac failure than in normal control rats in both order sequences (42 +/- 5 vs. 87 +/- 8%; 44 +/- 5 vs. 108 +/- 7%). In cardiac failure rats, vagotomy produced lesser increases (P < 0.05 for both) in renal sympathetic nerve activity than sinoaortic denervation in both order sequences (10 +/- 4 vs. 32 +/- 5%; 13 +/- 2 vs. 30 +/- 5%). The relative magnitude of impaired cardiac baroreceptor reflex function that is associated with the increased renal sympathetic nerve activity of cardiac failure is greater than that of impaired arterial baroreceptor reflex function.

Arterial and cardiopulmonary baroreflex control of renal nerve activity in cirrhosis.

Cirrhotic rats (common bile duct ligation; CBDL) have increased efferent renal sympathetic nerve activity (ERSNA), which contributes significantly to the observed renal sodium and water retention and edema formation. Basal ERSNA is increased and fails to suppress normally during intravenous isotonic saline volume expansion. Arterial and cardiopulmonary baroreflex control of ERSNA in CBDL and control (CTR) rats was examined. CBDL rats exhibited hyperdynamic circulation with increased cardiac index and decreased total peripheral resistance index and arterial pressure compared with CTR rats. Increases in left ventricular end-diastolic pressure (LVEDP) produced by volume expansion increased cardiac index normally in CBDL rats. The maximal gain of aortic baroreflex control of ERSNA was similar in CBDL and CTR rats. In CBDL rats, during decreased arterial pressure, there was a decreased range of the central component, which accounted for the decreased range of the overall aortic baroreflex, with the range of the afferent component being normal. For cardiopulmonary baroreflex control of ERSNA, the LVEDP threshold was increased and the gain was decreased in CBDL compared with CTR rats; this was due to an increased LVEDP threshold and a diminished gain of the afferent component while the central portion of the reflex was normal. These abnormalities in the cardiopulmonary baroreflex account for the attenuated decrease in ERSNA in CBDL compared with CTR rats during volume expansion. In CBDL rats, attenuation of cardiopulmonary baroreflex control of ERSNA contributes to both the increased basal ERSNA and its failure to normally suppress during volume expansion.

Reflex regulation of renal nerve activity in cardiac failure.

Efferent renal sympathetic nerve activity (ERSNA) is increased in the rat with low-cardiac-output congestive heart failure (CHF; myocardial infarction). Arterial and cardiopulmonary baroreflex control of ERSNA in CHF and control rats was examined. Cardiac index and arterial pressure were lower and total peripheral resistance index, left ventricular end-diastolic pressure, and heart-to-body weight ratio were higher in CHF than in control rats. Increases in left ventricular end diastolic pressure produced by intravenous volume loading failed to increase cardiac index in CHF rats as it did in control rats. Single-unit analysis of aortic baroreceptor nerve activity showed that CHF rats had higher pressure threshold, lower frequency at pressure threshold, and lower gain than control rats. Arterial baroreflex control of ERSNA was attenuated; this was due to diminished gain of the afferent limb while the gain of the central portion of the reflex was normal. Single-unit analysis of vagal nerve activity showed that CHF rats had higher pressure threshold, lower frequency at saturation, and lower gain than control rats. Cardiopulmonary baroreflex control of ERSNA was attenuated; this was due to diminished gain of the afferent limb while the gain of the central portion of the reflex was normal. In the CHF rat, arterial and cardiopulmonary baroreflex control of ERSNA is markedly attenuated because of abnormalities in the periphery at the level of the aortic and cardiopulmonary receptors, respectively, and not in the central nervous system.

Role of renal nerves in sodium retention of cirrhosis and congestive heart failure.

To define the role of renal nerves in renal Na retention of cirrhosis and congestive heart failure (CHF), experiments were done in rats with cirrhosis due to common bile duct ligation (CBDL) and CHF due to myocardial infarction from left coronary artery ligation. Two weeks after induction of CBDL or CHF, diseased and sham diseased (Sham) rats were subjected to bilateral renal denervation (DNX) or sham renal denervation (innervated, INN). Five days after DNX or INN, 26-day metabolic balance studies were carried out in all rats. Daily dietary Na intake averaged 2.0-3.0 meq/day on days 1-6 and 22-26 and averaged 0.120 meq/day on days 7-21. Cumulative Na balance was greater in CBDL and CHF rats, INN or DNX, than in Sham/CBDL or CHF rats throughout the study. On day 6 at the end of the normal dietary Na intake period (days 0-6), cumulative Na balance was not affected by renal denervation in Sham/CBDL or CHF rats (INN, 2.02 +/- 0.19 meq, n = 10; DNX, 2.04 +/- 0.17 meq, n = 11), CBDL rats (INN, 4.21 +/- 0.39 meq, n = 10; DNX, 3.78 +/- 0.37 meq, n = 10), or CHF rats (INN, 3.74 +/- 0.72 meq, n = 9; DNX, 3.22 +/- 0.55 meq, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)