Stimulation of cardiac sympathetic nerve activity by central angiotensinergic mechanisms in conscious sheep

Central actions of angiotensin play an important role in cardiovascular control and have been implicated in the pathogenesis of hypertension and heart failure. One feature of centrally or peripherally administered angiotensin is that the bradycardia in response to an acute pressor effect is blunted. It is unknown whether after central angiotensin this is due partly to increased cardiac sympathetic nerve activity (CSNA). We recorded CSNA and arterial pressure in conscious sheep, at least 3 days after electrode implantation. The effects of intracerebroventricular infusions of ANG II (3 nmol/h for 30 min) and artificial cerebrospinal fluid (CSF) (1 ml/h) were determined. The response to intracerebroventricular hypertonic saline (0.6 M NaCl in CSF at 1 ml/h) was examined as there is evidence that hypertonic saline acts via angiotensinergic pathways. Intracerebroventricular angiotensin increased CSNA by 23 +/- 7% (P < 0.001) and mean arterial pressure (MAP) by 7.6 +/- 1.2 mmHg (P < 0.001) but did not significantly change heart rate (n = 5). During intracerebroventricular ANG II the reflex relation between CSNA and diastolic blood pressure was significantly shifted to the right (P < 0.01). Intracerebroventricular hypertonic saline increased CSNA (+9.4 +/- 6.6%, P < 0.05) and MAP but did not alter heart rate. The responses to angiotensin and hypertonic saline were prevented by intracerebroventricular losartan (1 mg/h). In conclusion, in conscious sheep angiotensin acts within the brain to increase CSNA, despite increased MAP. The increase in CSNA may account partly for the lack of bradycardia in response to the increased arterial pressure. The responses to angiotensin and hypertonic saline were losartan sensitive, indicating they were mediated by angiotensin AT-1 receptors.     

Effect of angiotensin II and peptide YY on cerebral and circumventricular blood flow

Angiotensin II and peptide YY (PYY) are putative neuro/humoral agents acting at several circumventricular regions. These peptides also constrict cerebral vessels. We examined the effect of acute intravenous infusion of saline, angiotensin II and peptide YY on local cerebral blood flow (14C-iodoantipyrine autoradiography) in the circumventricular and non-circumventricular brain regions of 17 conscious rats. No reductions in brain blood flow (28 regions) were observed although angiotensin II and PYY infusion elevated arterial blood pressure 15-25% without influencing heart rate, suggesting an increase in peripheral resistance. However, local blood flow was dependent on the peptide infused. During PYY infusion, blood flow was rather constant in the 20 non-circumventricular regions examined whereas an increase in blood flow and a slight decrease in cerebrovascular resistance occurred in the circumventricular regions. The area postrema exhibited the most pronounced changes--an elevation in blood flow of 44 +/- 11% and a reduction in resistance of 20 +/- 5% in comparison to that in control animals. During angiotensin II infusion, local cerebral blood flow was similar to that in controls and local cerebrovascular resistance was elevated. Thus, the local cerebral circulatory response to peptide administration was dependent on the location of the region examined (circumventricular or non-circumventricular) and on the vasoactive peptide infused.     

Role of brain renin angiotensin system in neurodegeneration: An update

Renin angiotensin system (RAS) is an endocrine system widely known for its physiological roles in electrolyte homeostasis, body fluid volume regulation and cardiovascular control in peripheral circulation. However, brain RAS is an independent form of RAS expressed locally in the brain, which is known to be involved in brain functions and disorders. There is strong evidence for a major involvement of excessive brain angiotensin converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin type-1 receptor (AT-1R) axis in increased activation of oxidative stress, apoptosis and neuroinflammation causing neurodegeneration in several brain disorders. Numerous studies have demonstrated strong neuroprotective effects by blocking AT1R in these brain disorders. Additionally, the angiotensin converting enzyme 2 (ACE2)/Angiotensin (1–7)/Mas receptor (MASR), is another axis of brain RAS which counteracts the damaging effects of ACE/Ang II/AT1R axis on neurons in the brain. Thus, angiotensin II receptor blockers (ARBs) and activation of ACE2/Angiotensin (1–7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenerative diseases. Here in this review article, we discuss the expression of RAS in the brain and highlight how altered RAS level may cause neurodegeneration. Understanding the pathophysiology of RAS and their links to neurodegeneration has enormous potential to identify potentially effective pharmacological tools to treat neurodegenerative diseases in the brain.     

Chronic ICV infusion of neuropeptides alters lymphocyte populations in experimental rodents.

The sympathetic nervous system has been shown to influence immune function. Angiotensin II and substance P are two neurally active peptides that have been shown to increase sympathetic nervous system activity when injected centrally. Using osmotic minipumps, we chronically infused angiotensin II (1 microgram/h) and substance P (2 micrograms/h) into the brains of intact Sprague-Dawley rats for a period of 1 month and 2 weeks, respectively. Age-matched control animals were infused with artificial cerebrospinal fluid. We then examined the effect of this infusion on the percentage of different lymphocyte populations in the peripheral blood. The angiotensin II infused animals showed an increase in the percentage of total T-cells and a decrease in the percentage of B-cells relative to controls. The substance P treated animals also showed an increase in the percentage of T-cells present, but failed to show the decrease in the B-cell population seen with the angiotensin II infused group. This study shows that the central nervous system can influence the immune system. As shown in this study, these effects are most likely mediated via the sympathetic nervous system. These results add to the expanding body of data suggesting an important role of the central nervous in regulating immune function and our susceptibility to disease.     

Angiotensin biosynthesis and concentrations in brain of normotensive and hypertensive rats

We report here on the extraction and characterization of angiotensin I (ANG I) and angiotensin II (ANG II) from the brain of rats. High pressure liquid chromatography (HPLC) with different mobile phases combined with specific radioimmunoassays (RIA) proved to be a powerful tool for peptide characterization in biological samples; (Ile5)-ANG I, (Ile5)-ANG II and (Ile5)-ANG III could clearly be identified in cerebrospinal fluid (CSF), incubated in vivo and in vitro with renin, in total brain extracts, as well as in hypothalamus (HT), medulla oblongata (MO), cerebellum (CER) and cortex (CO). Angiotensin cleaved from CSF angiotensinogen and angiotensin extracted from brain showed retention times identical to those of plasma angiotensin and synthetic standard peptides, indicating that their amino acid sequence is probably identical. ANG I and ANG II were highest in the HT and lowest in the CO. Following bilateral nephrectomy (NX) both ANG I and ANG II persisted at control levels. Young 10 week old spontaneously hypertensive rats (SHRSP) showed significantly lower ANG I and ANG II concentrations in the HT compared with Wistar Kyoto rats (WKY). Intracerebroventricular (i.c.v.) administration of the converting enzyme inhibitor captopril caused a significant increase in ANG 1 in nephrectomized SHRSP but not in WKY. These differences were not found in 40 week old SHRSP. The data show that ANG I and ANG II are synthetized in the brain of rats. The lower concentrations and the enhanced accumulation of ANG I after converting enzyme blockade in nephrectomized young SHRSP indicate an increased turnover of angiotensin in hypertensive rats.     

Central hypertensive actions of angiotensin I, II and III in conscious rats

The effects of intracerebroventricular administrations of three natural angiotensins, angiotensin I (ANG I 3.8 X 10-11-9.4 X10-10 mol/kg body weight), II (9.6 X 10-12-2.4 X 10-10 mol/kg body weight) and III (2.7 X 10-10 2.5 X 10-9 mol/kg body weight) on systemic blood pressure were investigated in conscious rats. Angiotensin II (ANG II), ANG I and angiotensin III (ANG III), increased blood pressure in a dose-related manner. The order of potency of angiotensins was ANG II greater than ANG I greater than ANG III. The intraventricular administration of a converting enzyme inhibitor (SQ 14225, 6.9 X10-8 mol/kg) abolished the central effect of ANG I, while an angiotensin II analogue ([Sar1-Ala8]ANG II, 1.1 X 10-8 mol/kg) administered intraventricularly inhibited the central pressor effects of these three angiotensins. These results suggest that ANG II is a main mediator of the renin-angiotensin system in the central nervous system.     

Role of converting enzyme in the cardiovascular and adrenal cortical responses to (des-Asp1)-angiotensin I.

(Des-Asp1)-angiotensin I, angiotensin II and III were evaluated for pressor activities in conscious nephrectomized rats and for steroidogenic actions in rat adrenal zona glomerulosa. The pressor effect of this angiotensin nonapeptide was similar to that found with mole-equivalent doses of angiotensin III (one-third as active as angiotensin II) and was significantly attenuated by pretreatment with the 0. jararaca nonapeptide converting enzyme inhibitor. Hence, (des-Asp1)-angiotensin I is a substrate for converting enzyme in vivo, and the rapid conversion indicates that an alternate pathway for the formation of angiotensin III could exist. (Des-Asp1)-angiotensin I possessed only 0.1% of the activity of angiotensin III as a steroidogenic agent in cell suspensions of rat adrenal zona glomerulosa. Angiotensin I was a weak steroidogenic agent in vitro (1%) and was not blocked by an inhibitor of converting enzyme. Adrenal cells dispersed from the outer zone of the cortex would appear to be devoid of significant converting enzyme activity.     

Influence of brain angiotensin on thermoregulation and hydromineral balance during pregnancy in rats.

During mammalian pregnancy, body temperature decreases and there are changes in fluid and electrolyte balance. Angiotensin signaling mechanisms in the brain have been shown to influence thermoregulation and body fluid balance in the nonpregnant state. We hypothesized that brain angiotensin is also implicated in adjusting these physiological systems in the pregnant rat. We compared core temperature and fluid regulation in three groups of pregnant rats: untreated rats, rats receiving continuous infusion of an AT(1) antagonist candesartan (5 microg.kg(-1).day(-1)) into a lateral cerebral ventricle to block brain AT(1) receptors, and rats receiving vehicle [artificial cerebrospinal fluid (aCSF)] vehicle. Untreated and aCSF-treated rats showed a decrease in colonic temperature (-0.5 and -0.8 degrees C respectively) by day 20 of gestation. However, rats treated with candesartan had increased colonic temperature compared with baseline (+0.9 degrees C), and their temperature was significantly higher on days 7 (P < 0.05), 17 (P < 0.05), and 20 (P < 0.001) compared with the other groups (aCSF and untreated). Daily food and water intakes and body weight were not different between the three groups. Similarly, litter sizes and pup weights were equal in all groups. Finally, the expected decreases in plasma Na(+) and osmolality during pregnancy were equivalent in all groups. This study suggests that brain angiotensin mediates the progressive decrease in body temperature that occurs during pregnancy. However, the changes in fluid balance associated with pregnancy are not dependent on brain angiotensin.     

Changes in central and peripheral renin-angiotensin system after furosemide injection

To examine the effects of acute stimulation on the peripheral and central renin-angiotensin system, simultaneous sampling of blood and cerebrospinal fluid (CSF) for measurements of plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (PAng I-ir), plasma angiotensin II-immunoreactivity (PAng II-ir), plasma angiotensinogen and cerebrospinal fluid angiotensin II-ir (CSF Ang II-ir) and CSF angiotensinogen was carried out following intravenous injection of furosemide (5 mg/kg) in conscious dogs. Administration of furosemide induced marked increases in PRA, Ang I-ir, PAng II-ir and CSF Ang II-ir, however, neither plasma nor CSF angiotensinogen was changed. Furthermore, a relatively large dose (20 mg/kg/min) of intravenously infused synthetic Ang II for 20 min produced a five-fold increase in PAng II-ir compared with no significant increase in CSF Ang II-ir. In spite of significant suppression of PRA and PAng I-ir, there were no significant changes in either plasma or CSF angiotensinogen. These results primarily suggest that the peripheral and the brain renin-angiotensin systems may be linked and that acute changes in the peripheral renin-angiotensin system do not alter either plasma or CSF angiotensinogen.     

Central nervous effects of CRF and angiotensin II on cardiac output in conscious rats

Studies were performed to determine whether the central nervous system actions of corticotropin-releasing factor (CRF) and angiotensin II (ANG II) on systemic arterial pressure are mediated, in part, through changes in cardiac output (CO). Changes in CO after intracerebroventricular administration of ANG II and CRF were assessed in conscious unrestrained rats bearing pulsed Doppler flow probes on the ascending aorta. Intracerebroventricular injection of CRF (0.15 nmol) increased arterial pressure (15-20 mmHg), heart rate (70-100 beats/min), and CO (25-35%) without significantly affecting total peripheral resistance. Intracerebroventricular injection of ANG II (0.1 nmol) produced similar elevations of arterial pressure (15-20 mmHg). However, the ANG II-induced pressor response was attended by significant decreases in heart rate (20 beats/min) and CO (10-15%) and significant increases in total peripheral resistance (30-40%). The results of these studies demonstrate that CO, as assessed by pulsed Doppler flow probe methodology, may be influenced significantly and differentially by central nervous system administration of CRF and ANG II.     

Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats.

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA-NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA-NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA-NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.     

Lack of increase in concentrations of cerebrospinal fluid sodium in rats with various stages of DOCA-salt hypertension

Experiments were conducted in conscious rats to determine whether DOCA-salt treatment could cause an elevation of sodium concentration of cerebrospinal fluid (CSF), which may be responsible for the enhanced activity of sympathetic nervous system (SNS) and increased secretion of vasopressin (AVP). Systolic blood pressure (SBP) and mean arterial pressure (MAP) were gradually but consistently increased by DOCA-salt treatment. Serum Na concentration was similarly increased with time by DOCA-salt, and significantly higher than control in the 4th treatment week. In contrast, DOCA-salt did not alter the CSF Na levels at any time during treatment. A relationship between SBP and CSF Na was never evident at any stage of the DOCA-salt hypertension. The decrease in MAP following administration of the vasopressin V1-receptor antagonist, d(CH2)5Tyr(Me)AVP (30 micrograms/kg), or hexamethonium (30 mg/kg) was enhanced in the DOCA-treated rats, as compared to findings in the controls. These hypotensive effects were gradually, but progressively enhanced with the development of hypertension by DOCA-salt treatment. We tentatively conclude that mechanisms accounting for the enhanced activity of SNS and AVP in DOCA-salt hypertensive rats are independent of an increased Na concentration in the CSF.     

Physiological actions of angiotensin II on the kidney.

The importance of angiotensin as a modulator of renal function is well documented. Several lines of evidence suggest strongly that angiotensin plays an important role in the maintenance of renal vascular resistance and arterial pressure in several physiological and pathophysiological states with increased activity of the renin-angiotensin system. Angiotensin also acts as a physiological "brake" on excessive release of renin from juxtaglomerular cells. Angiotensin influences renal sodium excretion via its renal vascular actions to change the glomerular filtration rate and, thus, the filtered load of sodium; in addition, angiotensin influences tubular reabsorption of sodium by altering the filtration fraction and the balance of Starling forces in the peritubular capillaries.     

Enhanced sympathoexcitatory and pressor responses to central Na+ in Dahl salt-sensitive vs. -resistant rats

An enhanced responsiveness to increases in cerebrospinal fluid (CSF) Na+ by high salt intake may contribute to salt-sensitive hypertension in Dahl salt-sensitive (S) rats. To test this hypothesis, sympathetic and pressor responses to acute and chronic increases in CSF Na+ were evaluated. In conscious young (5-6 wk old) and adult (10-11 wk old) Dahl S and salt-resistant (R) rats as well as weight-matched Wistar rats, hemodynamic [blood pressure (BP) and heart rate (HR)] and sympathetic [renal sympathetic nerve activity (RSNA)] responses to 10-min intracerebroventricular infusions of artificial CSF (aCSF) and Na+-rich aCSF (containing 0.2-0.45 M Na+) were evaluated. Intracerebroventricular Na+-rich aCSF increased BP, RSNA, and HR in a dose-related manner. The extent of these increases was significantly larger in Dahl S versus Dahl R or Wistar rats and young versus adult Dahl S rats. In a second set of experiments, young Dahl S and R rats received a chronic intracerebroventricular infusion of aCSF or Na+-rich (0.8 M) aCSF (5 microl/h) for 14 days, with the use of osmotic minipumps. On day 14 in conscious rats, CSF was sampled and BP, HR, and RSNA were recorded at rest and in response to air stress, intracerebroventricular alpha2-adrenoceptor agonist guanabenz, intracerebroventricular ouabain, and intravenous phenylephrine and nitroprusside to estimate baroreflex function. The infusion of Na+-rich aCSF versus aCSF increased CSF Na+ concentration to the same extent but caused severe versus mild hypertension in Dahl S and Dahl R rats, respectively. After central Na+ loading, hypothalamus "ouabain" significantly increased in Dahl S and only tended to increase in Dahl R rats. Moreover, sympathoexcitatory and pressor responses to intracerebroventricular exogenous ouabain were attenuated by Na+-rich aCSF to a greater extent in Dahl S versus Dahl R rats. Responses to air-jet stress or intracerebroventricular guanabenz were enhanced by Na+-rich aCSF in both strains, but the extent of enhancement was significantly larger in Dahl S versus Dahl R. Na+-rich aCSF impaired arterial baroreflex control of RSNA more markedly in Dahl S versus R rats. These findings indicate that genetic control of mechanisms linking CSF Na+ with brain "ouabain" is altered in Dahl S rats toward sympathetic hyperactivity and hypertension.     

大鼠脑胆碱能系统对血量扩张引起利尿与尿钠排泄...

The role of brain cholinergic system on diuresis and natriuresis induced by volume expansion was studied in conscious rats. In a series of experiments, the diuretic, natriuretic and kaliuretic responses induced by volume expansion were compared in three groups of conscious rats pretreated respectively with intracerebroventricular (icv) injection of artificial cerebrospinal fluid (ACSF), atropine and hexamethonium. The natriuretic, kaliuretic and diuretic responses induced by volume expansion were much less in the animals with icv injection of atropine than in the control group with injection of ACSF (P less than 0.01). While the group pretreated with icv injection of hexamethonium showed no significant decrease in these responses of volume expansion than that of the control (P greater than 0.05). Volume expansion produced no change in insulin and PAH clearance in both the atropine and the ACSF group. Thus the atropine suppressed diuresis, natriuresis and kaliuresis are independent of changes in GFR and RPF. It is inferred from the results of the present investigation that volume expansion induced diuresis and natriuresis appear to be due to inhibition of water and sodium reabsorption in the renal tubules and regulated by certain brain cholinergic system.     

Focal metabolic effects of angiotensin and captopril on subregions of the rat subfornical organ

Angiotensin infusion increased glucose metabolism in 4 of 7 subdivisions of the rat subfornical organ, the effect being stronger in ventromedial compared to dorsolateral zones across the rostrocaudal axis. [Sar1-Leu8]Angiotensin II attenuated metabolic responses to intravenous angiotensin in all subfornical organ subregions. Brattleboro rats, having high circulating levels of angiotensin, displayed greater rates of glucose metabolism than Long-Evans rats in all subregions, differences that were eliminated by captopril, an inhibitor of angiotensin converting enzyme. The studies reveal focal subfornical organ zones where in vivo metabolic activity corresponds to cytoarchitectonic evidence for topographical processing within this angiotensin-sensitive structure.     

Respiratory effects of pressor and depressor agents in conscious rats

We hypothesized that the respiratory baroreflex in conscious rats is either more transient, or has a higher pressure threshold than in other species. To characterize the effect of arterial pressure changes on respiration in conscious rats, ventilation (V) was measured by the plethysmographic technique during injections, or infusions, of pressor and depressor agents. Bolus injections of angiotensin II (Ang II) or arginine vasopressin (AVP), transiently increased mean arterial pressure (MAP; mean +/- SE) 43+/-6 and 28+/-5 mm Hg (1 mm Hg = 133.3 Pa), respectively, and immediately reduced tidal volume (Vt) and, in the case of AVP, V. In contrast, by 10 min of a sustained elevation of MAP (40+/-3 mm Hg) with infusion of Ang II, Vt, f, and V were not different from control levels. Bolus injection of sodium nitroprusside (SNP) to lower MAP (-28+/-3 mm Hg) immediately increased breathing frequency (f) and V, whereas sustained infusion of SNP to lower MAP (-21+/-3 mm Hg) did not change for V at 10 and 20 min. In conscious rats, both injection and infusion of the pressor agent PE (+40 to 50 mm Hg) stimulated f and V; this contrasted with anesthetized rats where PE inhibited f and V, as reported by others. In conscious rats, respiratory responses associated with baroreflexes adapt rapidly and, in the case of PE, can be overridden by some other mechanism.     

Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat

Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.     

NO and endogenous angiotensin II interact in the generation of renal sympathetic nerve activity in conscious rats

Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats. However, whether NO tonically inhibits sympathetic outflow, or whether endogenous angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats is unknown. To address these questions, we determined the effects of NO synthase (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR) in conscious, unrestrained rats on normal (NS), high-(HS), and low-sodium (LS) diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When arterial pressure was kept at baseline with intravenous hydralazine, NOS inhibition with l-NAME (10 mg/kg i.v.) resulted in a profound decline in RSNA, to 42 +/- 11% of control (P < 0.01), in NS animals. This effect was not sustained, and RSNA returned to control levels by 45 min postinfusion. l-NAME also caused bradycardia, from 432 +/- 23 to 372 +/- 11 beats/min postinfusion (P < 0.01), an effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However, when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA after l-NAME infusion was absent in the LS rats, while the response in the HS group was unchanged by AIIRA. These findings indicate that, in contrast to our hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats, and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO is dependent on the action of endogenous ANG II.     

Motor Activity Increases Tryptophan, 5-Hydroxyindoleacetic Acid, and Homovanillic Acid in Ventricular Cerebrospinal Fluid of the Conscious Rat

An investigation was made into the effects of running (1 h at 20 m/min) on central serotonergic and dopaminergic metabolism in trained rats. Methodology involved continuous withdrawal of cerebrospinal fluid (CSF) from the third ventricle of conscious rats and measurements of tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels during a 2 h post-exercise period. All three compounds were increased during the hour following exercise and returned to their basal values within an hour later. CSF flow rate was stable when metabolite levels were elevated. Brain determinations indicated that CSF metabolite variations only qualitatively paralleled brain changes. Indeed, post-exercise TRP, 5-HIAA, and HVA levels were increased to a greater extent in brain when compared to CSF. It is suggested that increased serotonergic and dopaminergic metabolism, caused by motor activity, may be involved in the behavioral effects of exercise.