Consequences of the saphenous artery denervation under normal and chronically lowered blood pressure in rats

We studied constrictor responses of saphenous artery after sympathetic denervation in normotensive rats and rats with chronic regional hypotension. Abdominal aorta was partially occluded in Wistar rats distally to the renal arteries, lowering blood pressure in the hindquarters by about 40%, a week later to denervate saphenous artery the femoral nerve was cut. The density of periarterial nerve plexus and neurogenic responses of the vessel restored partially in 2 weeks and completely in 6 weeks after the surgery; the chronic hypotension did not modify the dynamics of reinnervation. Arteries of both groups of rats demonstrated higher sensitivity to noradrenaline during 6 weeks after denervation, whereas vessel sensitivity to serotonin was enhanced only in normotensive rats. Therefore, chronic hypotension may prevent postdenervation hypersensitivity of vascular smooth muscle to vasoconstrictors.     

Hepatoportal bumetanide-sensitive K(+)-sensor mechanism controls urinary K(+) excretion

To determine whether a K(+)-sensor mechanism exists in the hepatoportal region, periarterial hepatic afferent nerve activity responses to intraportal injection of KCl were examined in anesthetized rats. Hepatic afferent nerve activity increased in response to intraportal injection in a K(+) concentration-dependent manner, and the increase was attenuated by inhibition of the Na(+)-K(+)-2Cl(-) cotransporter by bumetanide in a dose-dependent manner. These results suggest that a bumetanide-sensitive K(+)-sensor mechanism exists in the hepatoportal region. Stimulation of this mechanism by intraportal KCl infusion elicited an immediate and powerful kaliuresis with no significant change in the plasma K(+) concentration; this was significantly greater than the kaliuresis induced by intravenous KCl infusion and was attenuated by severing the periarterial hepatic nervous plexus. These results indicate that a hepatoportal bumetanide-sensitive K(+)-sensor mechanism senses the portal venous K(+) concentration and that stimulation of this sensor mechanism causes kaliuresis, which is mainly mediated by the periarterial hepatic nervous plexus.     

Renorenal reflexes: interaction between efferent and afferent renal nerve activity.

In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure results in a contralateral inhibitory renorenal reflex response consisting of increases in ipsilateral afferent renal nerve activity, decreases in contralateral efferent renal nerve activity, and increases in contralateral urine flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To study possible functional central interaction among the afferent renal nerves and the aortic and carotid sinus nerves, the responses to renal mechanoreceptor stimulation were compared in sinoaortic denervated rats and sham-denervated rats before and after vagotomy. In contrast to sham-denervated rats, there was an increase in mean arterial pressure in response to renal mechanoreceptor stimulation in sinoaortic-denervated rats. However, there were no differences in the renorenal reflex responses among the groups. Thus, our data failed to support a functional central interaction among the renal, carotid sinus, and aortic afferent nerves in the renorenal reflex response to renal mechanoreceptor stimulation. Studies to examine peripheral interaction between efferent and afferent renal nerves showed that marked reduction in efferent renal nerve activity produced by spinal cord section at T6, ganglionic blockade, volume expansion, or stretch of the junction of superior vena cava and right atrium abolished the responses in afferent renal nerve activity and contralateral renal function to renal mechanoreceptor stimulation. Conversely, increases in efferent renal nerve activity caused by thermal cutaneous stimulation increased basal afferent renal nerve activity and its responses to renal mechanoreceptor stimulation. These data suggest a facilitatory role of efferent renal nerves on renal sensory receptors.     

Indomethacin attenuates post-suspension hypotension in Sprague-Dawley rats

Orthostatic hypotension is a serious condition that is sometimes manifested in astronauts during standing postflight. These observations may be related to impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. To evaluate the role of the cyclooxygenase inhibitor indomethacin as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-hr post-suspension period in conscious male Sprague-Dawley rats. Indomethacin (2 mg/kg) or saline were administered intravenously prior to release from suspension and at 2 and 4 hrs post-suspension. Direct MAP and heart rate were determined prior to suspension, daily and every 2 hrs post-suspension. During suspension, MAP did not change, in contrast, during post-suspension; it decreased compared to parallel non-suspended, untreated animals. There were no significant changes in heart rate. The reduction in MAP post-suspension was associated with significant increases in plasma prostacyclin. Indomethacin attenuated the observed post-suspension reduction in MAP and reduced plasma prostacyclin levels. Also, the baroreflex sensitivity for heart rate was modified by indomethacin--the MAP threshold for baroreflex activation was raised and the effective MAP range expanded. Thus, the post suspension reduction in mean arterial pressure may be due to overproduction of vasodilatory prostaglandins and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.     

Effect of two-week tail suspension on forelimb and hindlimb [correction of hindlimd] small arteries in rats

This study was aimed at comparing the effect of 2-week tail suspension on the characteristics of median artery and saphenous artery isolated from forelimb and hindlimb, accordingly. The segments of arteries were mounted in two-channel myograph for recording their isometric wall tension. In post-suspension rats segments of saphenous artery showed augmented sensitivity to noradrenaline and serotonin. More than two-fold decreased of EC50 was observed both before and after endothelium removal. Along with that, the sensitivity of median artery segments to vasoconstrictors was similar in post-suspension and control rats. However, the diameter of relaxed median artery in post-suspension rats was increased. Relaxation to acetylcholine compared to controls was augmented in both vascular regions of post-suspension rats being more pronounced in saphenous artery preparations.     

Post-suspension hypotension is attenuated in Sprague-Dawley rats by prostacyclin synthase inhibition

Cardiovascular deconditioning, sometimes manifested in astronauts during standing postflight, may be related to the impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-h post-suspension period in conscious male Sprague-Dawley rats to determine the role of prostacyclin in the observed post-suspension reduction in mean arterial pressure (MAP). The specific prostacyclin synthase inhibitor U-51605 (0.3 mg/kg), or saline, was administered intravenously prior to release from suspension and at 2 and 4 h post-suspension. During 7 days of suspension, MAP did not change, however, there was a post-suspension reduction in MAP which was associated with significant increases in plasma prostacyclin and nitric oxide. U-51605 attenuated the observed post-suspension hypotension and reduced plasma prostacyclin levels, but not nitric oxide levels. The baroreflex sensitivity for heart rate was modified by U-51605: increased MAP threshold and effective MAP range. Thus, the post-suspension reduction in mean arterial pressure may be due to overproduction of prostacyclin and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.     

Changes induced by angiotensins and prostaglandin E2 on the release of transmitter from isolated perfused rabbit kidney during periarterial stimulation.

The influence of A II and PGE2 on the rise of perfusion pressure induced by periarterial stimulation and NA were studied in the rabbit isolated perfused kidney. Periarterial stimulation produced an increase in perfusion pressure and the venous outflow superfusing the rabbit aortic strip caused the muscle to contract. Both effects were found to be frequency dependent. NA induced similar effect when given into the renal artery. A II and its N-terminal analogs produced equal potentiation to periarterial stimulation without altering the effect of exogenous NA when added to the perfusion medium. DMGIA II which is a competitive inhibitor of A II inhibited the potentiating affect of A II. PGE2 also inhibited the effect of A II without altering the effect of exogenous NA. Addition of aspirin to the perfusion medium caused a potentiation to periarteral stimulation but did not change the effect of NA. A II added to the perfusion fluid containing aspirin still caused potentiation. From these results it was concluded that: (i) A II-induced potentiation to periarterial stimulation is mediated via specific receptors and probably due to facilitation of the release of transmitter from sympathetic nerve ending. (ii) PGE2 inhibited the release of transmitter. The effect of A II and PGE2 seemed to be mediated by independent mechanisms.     

Attenuation of noradrenergic neurotransmission by the thromboxane synthetase inhibitor,UK 38,485

The purpose of this study was to determine the effects of chronic administration of the thromboxane synthetase inhibitor, UK 38,485, on noradrenergic neurotransmission. Male Sprague Dawley rats (n=14) were treated once daily with either UK 38,485 (100 mg/kg; n=7) or the vehicle of UK 38,485 (olive oil; n=7) by gavage. The dose of UK 38,485 chosen was sufficient to inhibit $\text{ex vivo}$ platelet TXB₂ production by >90% for 24 hours. One week into the treatment animals were prepared for $\text{in situ}$ perfusion of their mesenteric vascular beds. Vasoconstrictor responses to both exogenous norepinephrine and periarterial nerve stimulation were determined both before and during an infusion of angiotensin II (9ng/min) into the superior mesenteric artery. UK 38,485 significantly (P<0.02) attenuated the vascular response to periarterial nerve stimulation without altering the vascular response to either norepinephrine or angiotensin II. UK 38,485 did not influence the baseline perfusion pressure, the mean arterial blood pressure or the potentiation of neurotransmission by angiotensin II. These data indicate that in the $\text{in situ}$ rat mesentery UK 38,485 attenuates the release of neurotransmitter from sympathetic nerve terminals.     

Norepinephrine reuptake, baroreflex dynamics, and arterial pressure variability in rats

This study examined the effect of norepinephrine reuptake blockade with desipramine (DMI) on the spontaneous variability of the simultaneously recorded arterial pressure (AP) and renal sympathetic nerve activity (SNA) in conscious rats. Acute DMI administration (2 mg/kg iv) depressed AP Mayer waves ( approximately 0.4 Hz) and increased low-frequency (<0.2 Hz) components of AP variability. DMI decreased renal SNA variability, especially due to the abolition of oscillations related to Mayer waves. To examine whether DMI-induced changes in AP and renal SNA variabilities could be explained by alterations in the dynamic characteristics of the baroreceptor reflex loop, the frequency responses of mean AP to aortic depressor nerve stimulation were studied in urethan-anesthetized rats. DMI accentuated the low-pass filter properties of the transfer function without significantly altering the fixed time delay. The frequency responses of iliac vascular conductance to stimulation of the lumbar sympathetic chain were studied in an additional group of anesthetized rats. DMI did not markedly alter the low-pass filter properties of the transfer function and slightly increased the fixed time delay. These results suggest that the DMI-induced decrease in the dynamic gain of the baroreceptor reflex is responsible for the decreased spontaneous renal SNA variability and the accompanying increased AP variability. The "slowing down" of baroreflex responses cannot be attributed to an effect of DMI at the vascular neuroeffector junction.     

刺激肾神经传入纤维的降压反应与颈动脉窦压力感受性反射的相互作用

在麻醉兔,研究了刺激肾神经传入纤维与颈动脉窦压力感受性反射在减压反射中的相互作用。电刺激肾神经传入纤维引起平均动脉压(MAP)下降,下降程度在一定范围有赖于刺激频率。当颈动脉窦被隔离和主动脉神经切断后,随着颈动脉窦内压逐渐升高,刺激肾神经传入纤维引起的减压反应不断减弱。在45至135mmHg 之间的7个颈动脉窦内压(ISP)水平,刺激肾神经传入纤维,并画出刺激前和刺激时的 ISP-MAP 关系曲线。在颈动脉窦内压为75至105mmHg 之间,刺激肾神经传入纤维显著降低 ISP-MAP 关系曲线的斜率和对ISP 的平均动脉压反应范围。这些结果提示:(1)颈动脉窦压力感受器的传入冲动可调制刺激肾神经传入纤维的降压反应,在一定范围内与颈动脉窦内压呈反比;(2)刺激肾神经传入纤维明显减弱颈动脉窦的压力感受性反射。     

Coactivation of renal sympathetic neurons and somatic motor neurons by chemical stimulation of the midbrain ventral tegmental area

We examined whether neurons in the midbrain ventral tegmental area (VTA) play a role in generating central command responsible for autonomic control of the cardiovascular system in anesthetized rats and unanesthetized, decerebrated rats with muscle paralysis. Small volumes (60 nl) of an N-methyl-D-aspartate receptor agonist (L-homocysteic acid) and a GABAergic receptor antagonist (bicuculline) were injected into the VTA and substantia nigra (SN). In anesthetized rats, L-homocysteic acid into the VTA induced short-lasting increases in renal sympathetic nerve activity (RSNA; 66 ± 21%), mean arterial pressure (MAP; 5 ± 2 mmHg), and heart rate (HR; 7 ± 2 beats/min), whereas bicuculline into the VTA produced long-lasting increases in RSNA (130 ± 45%), MAP (26 ± 2 mmHg), and HR (66 ± 6 beats/min). Bicuculline into the VTA increased blood flow and vascular conductance of the hindlimb triceps surae muscle, suggesting skeletal muscle vasodilatation. However, neither drug injected into the SN affected all variables. Renal sympathetic nerve and cardiovascular responses to chemical stimulation of the VTA were not essentially affected by decerebration at the premammillary-precollicular level, indicating that the ascending projection to the forebrain from the VTA was not responsible for evoking the sympathetic and cardiovascular responses. Furthermore, bicuculline into the VTA in decerebrate rats produced long-lasting rhythmic bursts of RSNA and tibial motor nerve discharge, which occurred in good synchrony. It is likely that the activation of neurons in the VTA is capable of eliciting synchronized stimulation of the renal sympathetic and tibial motor nerves without any muscular feedback signal.     

Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats

Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.     

The effects of periarterial nerve activation on coronary vessel tone in an isolated and perfused slab of beef ventricle.

The direct effects of extrinsic nerve stimulation on coronary artery tone are unclear because of the complications arising from alterations in myocardial dynamics which themselves alter flow. An isolated and perfused nonbeating slab of beef ventricle was utilized in the present experiments to eliminate secondary complications and the efects of periarterial nerve activation on coronary perfusion pressure were examined. It was found that stimulation induced vasoconstrictor responses which were enhanced by physostigmine, a cholinesterase inhibitor, and blocked by atropine. These responses were duplicated by exogenous acetylcholine both in the perfused preparation and in isolated strips of coronary artery. Although added noradrenaline gave vasodilatation, no response attributable to the release of noradrenaline from nerves was obtained. It is concluded that the coronary vasculature of the beef receives a cholinergic innervation and that its activation, especially under conditions of reduced transmitter degradation, may induce considerable coronary vessel constriction.     

Effect of acute adrenalectomy on sympathetic responses to peripheral lipopolysaccharide or central PGE(2)

The impact of plasma corticosterone levels on the sympathetic nervous system (SNS) response to intravenous lipopolysaccharide (LPS) or intracerebroventricular injections of PG was studied in anesthetized (urethan-chloralose) male Sprague-Dawley rats. For this, electrophysiological recordings of splenic and renal nerves were completed in control or adrenalectomized (ADX) rats. LPS (10 microgram iv) similarly increased splenic and renal nerve activity in control rats with a shorter onset latency for the splenic nerve. Acute ADX enhanced the response of both nerves to LPS (P < 0.005) and reduced the onset latency of the renal nerve (P < 0.05). PGE(2) (2 microgram icv) rapidly increased the activity of both nerves but preferentially (magnitude and onset latency) stimulated the renal nerve (P < 0.05). The magnitude of the splenic nerve response to PGE(2) was unaffected by ADX. Unexpectedly, PGE(2) was less effective at stimulating renal nerve activity in ADX animals relative to intact controls (P < 0.05). Pretreatment of ADX rats with a CRF antagonist ([D-Phe(12), Nle(21,38), Calpha-MeLeu(37)]CRF-(12-41)) reversed this effect such that the renal nerve responded to central PGE(2) to a greater extent than the splenic nerve (P < 0.05), as was the case in non-ADX rats. These data indicate that enhanced sensitivity of central sympathetic pathways does not account for the enhanced SNS responses to LPS in ADX rats. Also, a CRF-related process appears to diminish renal sympathetic outflow in ADX rats.     

延髓头端腹外侧区一氧化氮与慢性心力衰竭大鼠心交感传入反射物的关系

为观察延髓头端腹外侧区(rostral ventrolateral medulla,RVLM)一氧化氮(N0)在慢性心力衰竭(chronic heart failure,CHF)大鼠增强的心交感传入反射(cardiac sympathetic afferent reflex,CSAR)中的作用,实验在去压力感受器神经支配的结扎冠状动脉诱发的CHF大鼠和假手术SD大鼠进行,记录电刺激心交感传入神经中枢端前后的血压和肾交感神经活动(renal sympathetic nerve activity,RSNA)变化以评价CSAR。结果显示：(1)CHF大鼠的CSAR显著增强;(2)RVLM微量注射NO合酶(NOS)抑制剂MeTC增强对照组大鼠的CSAR但对CHF大鼠的CSAR无显著影响;(3)RVLM微量注射NO供体S-nitroso-N-acetyl-penicillamine(SNAP)抑制CHF大鼠增强的CSAR;(4)S-methyl-L-thioeitruline（MeTC)仅增强对照组大鼠基础水平的RSNA,而SNAP抑制对照组和CHF大鼠基础水平的RSNA。结果表明RVLM中内源性NO的减少是导致CHF大鼠CSAR增强的重要机制之一。     

延髓头端腹外侧区一氧化氮与慢性心力衰竭大鼠心交感传入反射的关系

为观察延髓头端腹外侧区(rostral ventrolateral medulla,RVLM)一氧化氮(NO)在慢性心力衰竭(chronic heartfailure,CHF)大鼠增强的心交感传入反射(cardiac sympathetic afferent reflex,CSAR)中的作用,实验在去压力感受器神经支配的结扎冠状动脉诱发的CHF大鼠和假手术SD大鼠进行,记录电刺激心交感传入神经中枢端前后的血压和肾交感神经活动(renal sympathetic nerve activity,RSNA)变化以评价CSAR.结果显示:(1)CHF大鼠的CSAR显著增强;(2)RVLM微量注射NO合酶(NOS)抑制剂MeTC增强对照组大鼠的CSAR但对CHF大鼠的CSAR无显著影响;(3)RVLM微量注射NO供体S-nitroso-N-acetyl-penicillamine(SNAP)抑制CHF大鼠增强的CSAR;(4)S-methyl-L-thiocitmline(MeTC)仅增强对照组大鼠基础水平的RSNA,而SNAP抑制对照组和CHF大鼠基础水平的RSNA.结果表明RVLM中内源性NO的减少是导致CHF大鼠CSAR增强的重要机制之.     

Hemodynamic changes in post-suspension rats during gradual hemorrhage

We examined the changes of hemodynamic parameters in nembutal-anesthetized rats during gradual hemorrhage (2 ml/100 g body weight during 30 min). In control rats blood pressure began to decline starting from 3rd min of bleeding and from 5th min it was accompanied by cardiac deceleration. Hindlimb vascular resistance was only slightly increased up to 15th min (by 20-30%) and then began to grow drastically. Less prominent changes of hemodynamics were observed in post-suspension rats. The results indicate that when activity of sympathetic nervous system is blunted with anesthetic post-suspension rats demonstrate higher hemodynamic stability during acute hemorrhage.     

Developmental changes in neuromuscular transmission in the rat diaphragm.

Neuromuscular transmission was studied in diaphragms from rats of three ages, 4-7 days old, 11-12 days old, and adults with the use of an in vitro phrenic nerve-hemidiaphragm preparation. Each hemidiaphragm was stimulated via either muscle or nerve with 1-s stimulus trains at frequencies from 10 to 100 Hz. The patterns of force development obtained in response to the two routes of stimulation were compared for each group. Diaphragms from adults developed maximum force in response to stimulation of approximately 40 Hz with no significant decrease in force at higher frequencies. Within each stimulus train, once peak force was achieved, it was maintained for the remainder of the stimulus and responses to nerve and muscle stimulation were almost identical. In contrast, diaphragms from 4- to 7-day-old rats developed maximum force at approximately 20 Hz; stimulation at greater than or equal to 60 Hz induced significantly less peak force. This decrease in peak force at higher frequencies was significantly larger for nerve than for muscle stimulation. In addition, during each nerve stimulus train diaphragms from 4- to 7-day-old rats were unable to maintain peak force, which decreased at frequencies greater than 20 Hz. The decrease in force reached approximately 50% of peak at stimulation frequencies greater than or equal to 60 Hz. Diaphragms from 11- to 12-day-old rats showed intermediate responses. Based on the responses to phrenic nerve stimulation, we conclude that the neonatal rat diaphragm shows marked neuromuscular transmission failure that is not seen in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patterning of somatosympathetic reflexes reveals nonuniform organization of presympathetic drive from C1 and non-C1 RVLM neurons

To determine the organization of presympathetic vasomotor drive by phenotypic populations of rostral ventrolateral medulla (RVLM) neurons, we examined the somatosympathetic reflex (SSR) evoked in four sympathetic nerves together with selective lesions of RVLM presympathetic neurons. Urethane-anesthetized (1.3 g/kg ip), paralyzed, vagotomized and artificially ventilated Sprague-Dawley rats (n = 41) were used. First, we determined the afferent inputs activated by sciatic nerve (SN) stimulation at graded stimulus intensities (50 sweeps at 0.5-1 Hz, 1-80 V). Second, we recorded sympathetic nerve responses (cervical, renal, splanchnic, and lumbar) to intensities of SN stimulation that activated A-fiber afferents (low) or both A- and C-fiber afferents (high). Third, with low-intensity SN stimulation, we examined the cervical SSR following RVLM microinjection of somatostatin, and we determined the splanchnic SSR in rats in which presympathetic C1 neurons were lesioned following intraspinal injections of anti-dopamine-β-hydroxylase-saporin (anti-DβH-SAP). Low-intensity SN stimulation activated A-fiber afferents and evoked biphasic responses in the renal, splanchnic, and lumbar nerves and a single peak in the cervical nerve. Depletion of presympathetic C1 neurons (59 ± 4% tyrosine hydroxylase immunoreactivity profiles lesioned) eliminated peak 2 of the splanchnic SSR and attenuated peak 1, suggesting that only RVLM neurons with fast axonal conduction were spared. RVLM injections of somatostatin abolished the single early peak of cervical SSR confirming that RVLM neurons with fast axonal conduction were inhibited by somatostatin. It is concluded that unmyelinated RVLM presympathetic neurons, presumed to be all C1, innervate splanchnic, renal, and lumbar but not cervical sympathetic outflows, whereas myelinated C1 and non-C1 RVLM neurons innervate all sympathetic outflows examined. These findings suggest that multiple levels of neural control of vasomotor tone exist; myelinated populations may set baseline tone, while unmyelinated neurons may be recruited to provide actions at specific vascular beds in response to distinct stressors.     

Losartan corrects abnormal frequency response of renal vasculature in congestive heart failure

In congestive heart failure, renal blood flow is decreased and renal vascular resistance is increased in a setting of increased activity of both the sympathetic nervous and renin-angiotensin systems. The renal vasoconstrictor response to renal nerve stimulation is enhanced. This is associated with an abnormality in the low-pass filter function of the renal vasculature wherein higher frequencies (> or =0.01 Hz) within renal sympathetic nerve activity are not normally attenuated and are passed into the renal blood flow signal. This study tested the hypothesis that excess angiotensin II action mediates the abnormal frequency response characteristics of the renal vasculature in congestive heart failure. In anesthetized rats, the renal vasoconstrictor response to graded frequency renal nerve stimulation was significantly greater in congestive heart failure than in control rats. Losartan attenuated the renal vasoconstrictor response to a significantly greater degree in congestive heart failure than in control rats. In control rats, the frequency response of the renal vasculature was that of a first order (-20 dB/frequency decade) low-pass filter with a corner frequency (-3 dB, 30% attenuation) of 0.002 Hz and 97% attenuation (-30 dB) at > or =0.1 Hz. In congestive heart failure rats, attenuation did not exceed 45% (-5 dB) over the frequency range of 0.001-0.6 Hz. The frequency response of the renal vasculature was not affected by losartan treatment in control rats but was completely restored to normal by losartan treatment in congestive heart failure rats. The enhanced renal vasoconstrictor response to renal nerve stimulation and the associated abnormality in the frequency response characteristics of the renal vasculature seen in congestive heart failure are mediated by the action of angiotensin II on renal angiotensin II AT1 receptors.