Norepinephrine Stores Research Articles

Ischemic preconditioning fails to limit infarct size in reserpinized rabbit myocardium. Implication of norepinephrine release in the preconditioning effect.

Infarct size reduction by ischemic preconditioning is believed to be mediated by adenosine; however, whether adenosine is the factor responsible for the initiation of this protection remains unknown. It is possible that during preconditioning, adenosine stimulates receptors on presynaptic nerve terminals and retards the release of norepinephrine (NE) during the prolonged ischemia or that NE release during preconditioning augments adenosine production. To test whether the release of NE is involved in the preconditioning phenomenon, rabbits were pretreated with reserpine (5 mg/kg sc, 24 hours before) to deplete presynaptic nerve terminals of NE stores. On the day of the experiment, the rabbits were anesthetized with ketamine-xylazine and instrumented for coronary occlusion. Nonreserpinized animals were used as controls. The control group (n = 7) was subjected to 30 minutes of coronary occlusion and 120 minutes of reperfusion (ischemia-reperfusion) only. The preconditioned group (n = 10) received 5 minutes of preconditioning ischemia and 10 minutes of reperfusion before the prolonged ischemia-reperfusion. Of the reserpinized animals, half (n = 7) received preconditioning before ischemia-reperfusion and the remaining animals (n = 7) did not. At termination of the experiment, an intravenous tyramine challenge (1 mg/kg) was used to confirm NE depletion in reserpinized rabbits. The resulting infarcts were measured with tetrazolium and planimetry. With comparable hemodynamics and areas at risk, infarct size in control animals was 39.8 +/- 2.1% of the risk region. Preconditioned animals showed an expected reduction of infarct size to 14.8 +/- 2.2% of risk region (P < .05 vs control). Of the reserpinized animals, those that received reserpine alone had infarcts that were 38.5 +/- 4.5% of risk region, and those that were preconditioned had infarcts that were 41.4 +/- 3.6% of risk region, which was not significantly different than the control group. We conclude that preconditioning fails to protect ischemic-reperfused myocardium in reserpinized rabbit myocardium, indicating that the release of NE during either preconditioning or prolonged ischemia is critical to preconditioning mediated protection.

Effects of GM1 ganglioside on cardiac function following experimental hypoxia-reoxygenation

Rat hearts made hypoxic for 20 min by perfusion with 95% N 2/5% CO 2 and reoxygenated for 20 min in a Langerdorff apparatus showed a dose-dependent reduction of lactate dehydrogenase release when incubated with ganglioside GM1 (0.1–10 mu;M). The decline of contractile force during hypoxia was also reduced dose dependently in the presence of GM1. Similar effects were observed in hearts obtained from animals treated i.p. with 40 mg/kg GM1 for 14 days. The levels of Na +, K +-ATPase in ventricular tissue were also reduced after hypoxia-reoxygenation and the reduction was prevented in hearts from GM1-treated animals. GM1 (1–30mu;M) reduced the functional response to field stimulation of adrenergic nerve terminals in isolated atria. Rat atria made hypoxic in glucose-free media maintained normal stores of tissue noradrenaline in the presence of 1 mu;M GM1. In the rabbit, GM1 (40 mg/kg i.p. for 4 days) reduced the alterations of the ST segment of the ECG during acute occlusion of the left descending and circumflex coronaries artery. In conclusion, ganglioside GM1 reduces some effects of hypoxia-reoxygenation in the heart, through still unknown mechanisms.

Neurotransmitter release mechanisms at the sympathetic neuroeffector junction.

CONTENTS PAGE Introduction 591 The quantal hypothesis 592 The vesicular hypothesis 593 Anatomical considerations 593 Intercellular relationships 593 Innervation 594 Sympathetic neurotransmitters 595 Early studies of transmitter release from postganglionic sympathetic nerves 595 Biochemical studies of noradrenaline storage and secretion 596 How much noradrenaline is released from the average varicosity by an action potential? 598 Electrophysiological studies of transmitter release mechanisms at the level of the individual varicosity 598 Intermittent transmitter release 599 ATP as a neurotransmitter at the sympathetic neuroeffector junction 601 Why is transmitter release intermittent? 602 Active or passive invasion of nerve terminals by action potentials 605 Biochemistry of depolarization-secretion coupling 606 Chemical modulation of sympathetic neurotransmission 607 Comparison with other neuromuscular junctions and synapses 609 Concluding remarks 610 References 610

Changes in sympathetic nerve terminals in the heart of cold-exposed rats.

Changes in sympathetic nerve terminals of the heart after varying periods of exposure of rats to 4 degrees C were investigated. Two indices were used for changes in the number of noradrenaline storage vesicles, i.e., vesicular dopamine beta-hydroxylase (DBH) activity and noradrenaline storage capacity. The latter was obtained after uptake of [3H]noradrenaline; endogenous content, uptake of exogenous noradrenaline, and degree of saturation of the vesicles were calculated using the specific activity of the [3H]noradrenaline. As a measure of tyrosine hydroxylase activity, whole ventricular noradrenaline, dopamine, and dihydroxyphenylacetic acid content were used. After 4 h of cold exposure there was an increase in vesicular endogenous noradrenaline content, uptake, storage capacity, and DBH activity as well as a large increase in whole ventricular dopamine. After 6 h in the cold, vesicular endogenous noradrenaline content, storage capacity, and DBH activity were decreased. The results suggest that during cold exposure there is an initial increase followed by a decrease in the number of functional vesicles in the nerve terminal, which could explain the fluctuations in the rate of noradrenaline release.

Prehepatic portal hypertension in rats modifies norepinephrine metabolism in hypothalamus medulla oblongata and portal vein

The present experiments investigated the possible relationship between portal hypertension and norepinephrine metabolism in the central nervous system (hypothalamus and medulla oblongata) and the portal vein in the rat. Group I (72), portal hypertensive, and group II (70) sham-operated animals, were sacrificed day 14, and endogenous norepinephrine content, uptake and release from hypothalamus, medulla oblongata, and portal vein were investigated. In group I our results showed increases in norepinephrine storage (69%; 8.3%) and release (19.7%; 43.8%) and a diminished uptake (42.3%; 27.5%) in the hypothalamus and medulla oblongata, respectively. Portal veins showed a decreased content and uptake (62.5% and 43.5%, respectively) and increased release (25%) compared to group II rats. These results suggest a close relationship between the central nervous system and rat portal hypertension, perhaps related to modifications of central sympathetic activity.

Regional differences in sympathetic reinnervation after human orthotopic cardiac transplantation.

In the majority of humans > or = 1 year after cardiac transplantation, cardiac norepinephrine (NE) stores reappear, suggesting late sympathetic reinnervation. To determine whether there are regional differences in reinnervation, we measured markers of sympathetic reinnervation of the sinus node (SN) and left ventricle (LV) in five early transplant recipients (< or = 4 months after cardiac transplantation), 45 late transplant recipients (> or = 1 year after cardiac transplantation), and seven normally innervated control patients. SN reinnervation was defined as an increase in heart rate by more than five beats per minute after injection of tyramine into the artery supplying the SN. LV reinnervation was defined as a measurable LV NE release after left main coronary injection of 8 micrograms/kg tyramine. In 13 patients with previously known LV reinnervation, regional LV reinnervation was assessed by NE release after subselective injection of tyramine (4 micrograms/kg) into the proximal left anterior descending and circumflex arteries. Five of five patients < or = 4 months after cardiac transplantation had no change in heart rate and no LV NE release, confirming early, total denervation. In contrast, > or = 1 year after cardiac transplantation, tyramine caused a heart rate increase (eight to 49 beats per minute) in 32 of 45 patients and LV NE release in 33 of 45. Although LV NE release was correlated with the change in heart rate in late cardiac transplantation recipients (r = .61), eight of 45 had only heart rate response, nine had only LV NE release, and four had neither. In late cardiac transplantation recipients with LV reinnervation, tyramine caused NE release from both the anterior descending and circumflex perfusion fields in 10 of 14, but one of 14 patients released NE only after circumflex tyramine and three of 14 only after left anterior descending tyramine stimulation. Tyramine caused a marked heart rate increase and LV NE release in all control patients. Sympathetic reinnervation after cardiac transplantation is regionally heterogeneous. SN reinnervation is not associated necessarily with LV reinnervation, and LV reinnervation can involve the anterior and posterior walls together or separately.

Abnormal stress responses in patients with diseases affecting the sympathetic nervous system.

Diseases that cause malfunction of the sympathetic nervous system provide insight into how the sympathetic nerves normally modulate responses to stress. This paper discusses insight from a number of such diseases. Transection of the cervical spinal cord leads to autonomic dysreflexia. This syndrome causes episodic hypertension in quadriplegic patients from excess sympathetic activity reflexly activated by bowel or bladder distention. These patients lack cerebral control of spinal sympathetic reflexes. Radiotherapy to the neck can destroy the arterial baroreceptors that monitor blood pressure fluctuations. Patients who lack baroreceptors have exaggerated blood pressure responses to stress. They have episodes of hypertension and hypotension that cause headaches and dizziness. Diabetics and uremics often develop a peripheral sympathetic neuropathy. They have postural hypotension and diminished blood pressure responses to stress. They are often unable to tolerate heat, exercise, or fluid deprivation. Patients with heart failure deplete sympathetic neuronal norepinephrine stores. The continual stress of heart failure diminishes their ability to respond to further stresses such as standing upright or exercising. Patients with diseases of the sympathetic nervous system illustrate that everyday occurrences such as a change in posture or ambient temperature are stresses requiring a marked change in sympathetic nervous activity. Both physical and psychological stresses elicit large initial sympathetic neuronal responses that are subsequently damped by feedback inhibition from structures such as the baroreceptors. Damage to part of these feedback loops leads to exaggerated pressor responses to stress.

Pharmacological separation of cardio-accelerator and vagal inhibitory capacities of sympathetic nerves

Prolonged attenuation of vagal action at the heart, proposed to be due to release of the sympathetic cotransmitter neuropeptide Y (NPY), follows stimulation of cardiac sympathetic nerves. It has been shown that pretreatment with reserpine depletes cardiac and neuronal stores of both noradrenaline and NPY, while combined pretreatment with reserpine and the ganglion blocking agent chlorisondamine reduces depletion of NPY, while still depleting noradrenaline. The effects of reserpine pretreatment and combined chlorisondamine and reserpine pretreatment on the inhibition of cardiac vagal action evoked by cardiac sympathetic nerve stimulation (16 Hz, 2 min) were compared in anaesthetised dogs. In dogs with no pretreatment ( n = 6), sympathetic stimulation evoked an immediate cardio-acceleration, and a prolonged inhibition of cardiac vagal action, with a maximum percent inhibition (MPI) and time to half-recovery (T 50) of 78 ± 6% and 16 ± 2 min respectively. In dogs pretreated with reserpine ( n = 6, 1 mg/kg, 24 h), the immediate cardio-acceleration (ANOVA, P < 0.01), and the magnitude (MPI = 31.8%, ANOVA, P < 0.001) and duration (T 50 = 6 ± 1 min, ANOVA, P < 0.05) of inhibition of cardiac vagal action following sympathetic stimulation were significantly attenuated. In dogs with combined chlorisondamine ( n = 5, 2 mg/kg, 48 and 24 h) and reserpine pretreatment, there was again significantly reduced cardio-acceleration (ANOVA, P < 0.01), but the inhibition of cardiac vagal action following sympathetic stimulation did not significantly differ from untreated animals (MPI = 79 ± 8%, T 50 = 21 ± 6 min). Intravenous injections of NPY (25–50 μg/kg) evoked prolonged inhibition of cardiac vagal action in untreated and both groups of pretreated animals. These experiments indicate that the cardio-accelerator and vagal inhibitory capacities of sympathetic nerve stimulation can be separated, and are consistent with the sympathetic vagal inhibitory factor being NPY.

Impaired acquisition of novel locomotor tasks in aged and norepinephrine-depleted F344 rats

Performance of rats on a motor learning paradigm that has been demonstrated to be dependent upon cerebellar norepinephrine (NE) was studied in 20-month-old F344 rats. The behavioral task is identical to that described by Watson and McElligott: Rats are trained on a runaway consisting of aluminum pegs arranged in a regular pattern. Rats receive a water reward at either end of the runaway. Subsequent to training, rats are tested for running times on a runway with irregularly spaced rods. The ability of rats to improve their performance (decrease their running times) on this novel motor task is diminished in young rats that have received 6-hydroxydopamine lesions. Rats at 20 months of age are known to have deficits in cerebellar noradrenergic transmission; thus, the hypothesis to be tested was to determine if aged rats demonstrated performance deficits similar to young rats depleted of central stores of NE. The rate of acquisition of the task was determined by the decrease in running times with successive days of training. The ability of 20-month-old F344 rats to acquire proficiency on the novel motor task was impaired and the rate of acquisition of the novel motor task was not different from the young 6-hydroxydopamine-lesioned rats. In an attempt to distinguish between alterations in motor coordination and motor learning, additional tests of psychomotor performance were assessed for all groups of rats. These tests included a walking on 2.5- and 5-cm rods, speed of running on the motor task, and number and types of mistakes made on the motor learning task. The data indicate that none of the above-mentioned factors correlated with the ability of an individual rat to learn the novel motor task, suggesting age-related motor performance deficits may be separable from motor learning deficits. This data is consistent with our hypothesis that age-related alterations in noradrenergic function may underlie the decline in motor learning.

The effects of thapsigargin on [Ca2+]i in isolated rat mesenteric artery vascular smooth muscle cells.

The effects of thapsigargin were studied on single cells isolated from side branches of the rat mesenteric artery. Thapsigargin (150 nM) produced a transient increase of [Ca2+]i. This transient rise of [Ca2+]i was unaffected by removing external Ca2+ ions. This suggests that thapsigargin is releasing Ca2+ ions from an intracellular store. In the absence of thapsigargin both noradrenaline and caffeine also produced a transient increase of [Ca2+]i. These increases were abolished by prior exposure to thapsigargin. Correspondingly, the effects of thapsigargin were abolished by prior exposure to caffeine. These results show that thapsigargin releases Ca2+ from the noradrenaline and caffeine-sensitive stores.

Norepinephrine content in cardiovascular tissues from the aged Fischer 344 rat.

The major aim of the present study was to examine cardiovascular tissues and to determine if norepinephrine (NE) stores declined in aged (22-30 months old) male Fischer 344 (F344) rats. NE content was measured by HPLC in the whole heart, ventricle, atria, caudal artery, renal arteries, portal vein and kidney. The release of [3H]NE from the caudal artery of adult and aged rats was assessed as a functional index of sympathetic innervation. Renal alpha 2-adrenergic binding sites were also determined using 2.0 nM [3H]rauwolscine. In general, total NE content per organ was not altered in aged rats. The exception was the ventricle of aged rats which exhibited a 25% decrease in NE content. In contrast, NE content per gram of tissue weight was significantly decreased in the whole heart, atria, ventricle, kidney and caudal artery of aged rats when compared to that of adults (6-8 months old). Neither basal nor potassium-stimulated NE release was altered in the caudal artery of aged rats. Presynaptic regulation of NE release by taurine and alpha 2-adrenoceptors was also not affected by age. Renal alpha 2-adrenergic binding sites were decreased 23% in aged rats. Tissue growth that occurs as a function of aging does not appear to receive a concomitant increase in sympathetic growth as indexed by NE content. The findings of the present study would lead to the conclusion that with the exception of the ventricle, sympathetic nerve terminals of the aged male F344 rat are relatively intact.

Myocardial catecholamine and neuropeptide Y depletion in failing ventricles of patients with idiopathic dilated cardiomyopathy. Correlation with beta-adrenergic receptor downregulation.

Myocardial adrenergic neurotransmitters and beta-adrenergic receptor levels were measured in left and right ventricular myocardial specimens obtained from 30 patients with biventricular failure resulting from idiopathic dilated cardiomyopathy. Nonfailing myocardium obtained from 12 organ donors provided control data. Norepinephrine, dopamine, and neuropeptide Y concentrations were significantly decreased in failing compared with nonfailing control hearts. The mean ratio of dopamine to norepinephrine and of dopamine to neuropeptide Y in failing hearts was also significantly decreased compared with nonfailing control hearts. Compared with nonfailing control hearts, Bmax and beta 1-receptor density were significantly decreased in failing hearts and there were weak but significantly positive correlations of Bmax and beta 1-adrenergic receptors with norepinephrine, dopamine, and neuropeptide Y. Norepinephrine and its cotransmitter neuropeptide Y are depleted in failing human ventricular myocardium. Decreased norepinephrine stores correlate weakly with beta 1-adrenergic receptor downregulation consistent with the hypothesis that norepinephrine depletion occurs in response to increased adrenergic drive. Decreased dopamine relative to norepinephrine implies that an abnormality of dopamine conversion to norepinephrine is not present in failing human heart.

The effect of verapamil on cardiac sympathetic function

We have used systolic time intervals (STI) to measure inotrophy and chronotropy as indirect measures of the actions of noradrenaline, in order to ascertain whether the depletion of cardiac noradrenaline stores which has been shown to occur in laboratory rats after chronic verapamil treatment could be demonstrated in healthy volunteers. Placebo, verapamil, or atenolol were given by slow intravenous injection to 8 healthy volunteers and QS2I, LVETI, and PEP/LVET were measured. Verapamil pretreatment resulted in a positive inotropic state. Intravenous verapamil after oral pretreatment caused accentuated negative inotropic and chronotropic responses as compared with acute verapamil without pretreatment. We postulate that the observed initial inotropic effect may be in part due to an increase in the amount of noradrenaline available to the myocardium intrasynaptically, and that the accentuated negative response after intravenous or oral verapamil may result from a decrease in cardiac noradrenaline storage.

Carrier-mediated outward transport of dopamine from adrenergic varicosities of the vas deferens of reserpine-pretreated rats

In vasa deferentia of reserpine-pretreated rats a carrier-mediated (i.e., desipramine-sensitive) outward transport of endogenous dopamine was induced by either tyramine or ouabain. The dopamine taking part in the efflux induced by tyramine (and the concomitant efflux of DOPAC) was derived from ongoing synthesis of dopamine. Inhibition of MAO trebled the rate of spontaneous efflux of dopamine and reduced the spontaneous efflux of DOPAC by 90%. After inhibition of MAO, desipramine caused a further five-fold increase in the basal efflux of dopamine with no change in the basal efflux of DOPAC. Inhibition of COMT failed to affect the spontaneous efflux of dopamine but increased that of DOPAC. It is concluded that, after depletion of the noradrenaline stores by pretreatment with reserpine, an outward transport of axoplasmic dopamine is induced by the same mechanisms that (without any pretreatment with reserpine) are known to initiate an outward transport of noradrenaline.

Decreased norepinephrine release in anterior hypothalamus of NaCl-sensitive spontaneously hypertensive rats during high NaCl intake

We previously demonstrated that dietary NaCl supplementation reduces endogenous norepinephrine stores and turnover in the anterior hypothalamic area (AHA) of male NaCl sensitive spontaneously hypertensive rats (SHR-S) but not in NaCl resistant control rats and have implicated this mechanism in the pathogenesis of NaCl sensitive hypertension. In the current study, we tested directly the hypothesis that dietary NaCl supplementation decreases the release of norepinephrine from nerve terminals in the AHA of SHR-S using the push-pull perfusion technique. Conscious, freely moving SHR-S and control Wistar-Kyoto (WKY) rats were studied after 2–3 weeks of 8% or 1% NaCl feeding. In the 1% NaCl fed SHR-S, 3-methoxy-4-hydroxyphenylglycol (MOPEG, the major metabolite of norepinephrine in brain) levels averaged 272 ± 32 pg/10 min; norepinephrine levels, 17 ± 2 pg/10 min; in the 8% NaCl fed SHR-S, MOPEG levels averaged 72 ± 7 pg/10 min; norepinephrine levels were 6 ± 1 pg/10 min. There was a positive linear correlation ( r = 0.77; P < 0.01) between MOPEG and norepinephrine levels in AHA perfusates, indicating that perfusate MOPEG levels provide a useful index of norepinephrine release from AHA nerve terminals. In contrast, MOPEG levels in AHA perfusates were not affected by dietary NaCl intake in control WKY, and in control posterior hypothalamic perfusates, were not affected by dietary NaCl intake in SHR-S. These results give the first direct evidence that dietary NaCl supplementation is associated with greatly reduced norepinephrine release from nerve terminals in the AHA in SHR-S, but not in WKY controls, supporting the hypothesis that NaCl sensitive hypertension in this model is mediated by a NaCl induced reduction in AHA mediated inhibition of sympathetic outflow.

Altered myocardial acetylcholine and norepinephrine concentrations in right ventricular hypertrophy and failure

The progression of cardiac hypertrophy and failure is associated with marked changes in cardiac autonomic innervation, and there are sympathetic-parasympathetic interactions in the regulation of cardiac function. Although the indexes of sympathetic innervation have been found to be depressed with the development of heart failure, those of parasympathetic innervation have not yet been fully investigated. In order to better understand changes in markers of autonomic innervation associated with cardiac hypertrophy and failure, we measured the myocardial acetylcholine (ACh) store as a parasympathetic marker and the norepinephrine (NE) store as a sympathetic marker in pressure-overloaded right ventricular hypertrophy in rats. Two weeks after the injection of monocrotaline, significant right ventricular hypertrophy occurred. Three weeks after, severe right ventricular hypertrophy with no sign of heart failure occurred, and 4 weeks after, overt heart failure developed. In the right heart of monocrotaline rats, NE concentrations tended to increase at 1 week, returned to baseline at 2 weeks, decreased to one-half of the control values at 3 weeks, and then fell to 14% of the controls at 4 weeks. ACh concentrations in the right heart tended to increase at 1 week and exhibited a significant increase (136% and 129% of the controls in the right atrium and ventricle, respectively) at 2 weeks. As with NE, ACh concentrations in the right atrium and ventricle decreased to 76% and 54% of the controls at 3 weeks, and continued to decrease to 22% and 24% of the controls at 4 weeks after monocrotaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of repeated immobilization stress on the uptake of exogenous [ 3H]dopamine in adrenal chromaffin cells of mice

Uptake of [ 3H]dopamine in adrenal chromaffin cells of the mouse during repeated immobilization was examined by autoradiography. Repeated daily immobilization of mice resulted in an increased uptake of [ 3H]dopamine to the level of denervated chromaffin cells. The increase was observed only in adrenaline-storing (A) cells, not in noradrenaline-storing (NA) cells. The results indicate that sympathetic outflow to the adrenal gland, especially to A cells, is ceased or blocked during the adaptation to stress.

Noradrenaline turnover and metabolism in myocardium following aortic constriction in rats

The aim was to provide meaningful information on the function of the sympathetic system soon after an increased pressure overload on the heart. Noradrenaline storage, turnover, uptake, and synthesis were investigated at 3, 14, and 28 d after aortic banding in rats. Sham operated rats without aortic banding were used as control group. Left ventricle, spleen, and kidney from male Sprague-Dawley rats (175-200 g) were used in this study. Cardiac noradrenaline concentration was decreased at 3 d and 28 d after banding and increased at 14 d; left ventricular mass was increased from 14 d onwards. The rate of change in the specific activity of myocardial noradrenaline (noradrenaline turnover) as well as dopamine beta hydroxylase, an enzyme for noradrenaline synthesis, was unaltered at 3 d, increased at 14 d, and decreased at 28 d after aortic banding. Myocardial [3H]noradrenaline uptake, on the other hand, was decreased at all time points studied. The changes observed in the myocardium at day 14 were specific since noradrenaline turnover rate was unaltered in other peripheral organs such as spleen and kidney. Furthermore, after ganglionic blockade with pentolinium, both sham operated control and banded animals had identical, low noradrenaline turnover rate constants, and significant restoration of cardiac weight and noradrenaline stores was observed in the hearts from banded animals. Noradrenaline turnover and metabolism are altered soon after imposing increased workload on heart. Whether or not the changes in the sympathetic activity are a prerequisites for hypertrophy still remains to be seen.

The Influence of Dietary Restriction, Germ-Free Status, and Aging on Adrenal Catecholamines in Lobund-Wistar Rats

Adrenal catecholamines (CA) were measured in 6-, 18-, and 30-mo Lobund-Wistar rats (LWR) maintained under germ-free or conventional conditions and fed either ad libitum or a restricted (70% of adult ad libitum) diet. Levels of dopamine (DA), norepinephrine (NE), epinephrine (E), and dihydroxymandelic acid (DHMA) were determined by HPLC-EC. Compared with values from 6- and 18-mo rats, mean adrenal weight, DA and NE content and concentration, and E content were increased in the 30-mo rats; E concentration was not. The ratio of E:NE declined in the 30-mo group. Germ-free status and dietary restriction had little effect in modulating these age-related changes. Reanalysis of adrenal weights of 30-mo rats revealed two clear subgroups, hyperplastic and non-hyperplastic; the data from hyperplastic adrenals revealed an exaggerated form of the "aged" CA profile, whereas data from the nonhyperplastic adrenals more closely resembled that of younger rats. Thus, aging in LWR is associated with adrenal hyperplasia and a tendency toward elevated adrenomedullary stores of DA and NE, while E stores are maintained near levels found in young rats.

Dietary Ca2+prevents NaCI-sensitive hypertension in spontaneously hypertensive rats via sympatholytic and renal effects

NaCl-sensitive spontaneously hypertensive rats (SHR-S) were used to test the hypotheses that dietary Ca2+ supplementation 1) prevents NaCl-sensitive hypertension via a sympatholytic mechanism, and 2) increases diuretic and natriuretic responses to acute volume loading. SHR-S and control WKY rats were begun on one of four diets at age 8 wk: control, high NaCl, high Ca2+, or high NaCl and high Ca2+. In SHR-S, dietary Ca2+ supplementation prevented the NaCl-induced increases in blood pressure and plasma norepinephrine concentrations, the reductions in anterior hypothalamic norepinephrine stores and turnover, and the secondary increases in alpha 2 adrenoceptor number. Thus, Ca2+ prevented NaCl-sensitive hypertension in SHR-S by increasing noradrenergic input to the anterior hypothalamus. High-NaCl-fed SHR-S had impaired diuretic and natriuretic responses to an isotonic volume load; Ca2+ enhanced the ability of these animals to adjust fluid volume rapidly via diuresis and natriuresis. This alteration in renal function may contribute to the hypotensive effect of a high Ca2+ diet in NaCl-sensitive hypertension.