Effects of simultaneous diabetes and hypertension in an insulin dependent diabetic model.

Several lines of evidence suggest that hypertension is a contributing factor to diabetic nephropathy, a major cause of mortality in diabetes mellitus patients. The present study tested the hypotheses (1) that insulin dependent diabetes (IDD) causes hypertension, and (2) that simultaneous hypertension and IDD causes greater renal damage than would be expected from the independent contributions of each disease. IDD was induced by injection of streptozotocin (STZ, 65 mg/kg i.

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.

Central vasopressin receptors are upregulated by deoxycorticosterone acetate.

Studies were performed to characterize the regulation of central vasopressin (AVP) receptors in deoxycorticosterone acetate (DOCA)-NaCl-treated and control rats, and in DOCA-treated primary neuronal enriched cell cultures. Uninephrectomized rats were given NaCl to drink and implanted subcutaneously with a silastic implant containing 200 mg/kg DOCA. [3H]AVP binding to a diencephalic block of tissue was examined.

Intrahypothalamic clonidine infusion prevents NaCl-sensitive hypertension.

We have previously shown that dietary NaCl supplementation increases blood pressure and sympathetic nervous system activity in association with decreased norepinephrine release and increased alpha 2-adrenergic receptor number in the anterior hypothalamic area of salt-sensitive spontaneously hypertensive rats (SHR-S) but not in salt-resistant spontaneously hypertensive rats (SHR-R) or Wistar-Kyoto (WKY) rats. Further, acute microinjection of clonidine into the anterior hypothalamic area produced depressor responses that were augmented by high salt feeding in SHR-S but not in SHR-R or WKY rats. The current study tested the hypothesis that chronic infusion of clonidine into the anterior hypothalamic area prevents salt-sensitive hypertension in SHR-S.

Dietary Ca2+ prevents NaCl-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.

High-NaCl diets increase natriuretic and diuretic responses in salt-resistant but not salt-sensitive SHR.

This study tested the hypothesis that NaCl-sensitive spontaneously hypertensive rats (SHR-S) display a defect in natriuretic and diuretic responses to acute volume loading that contributes to the rise in arterial pressure observed when the rats are fed a high-NaCl diet. Seven-week-old SHR-S and NaCl-resistant SHR rats (SHR-R) and normotensive (Wistar-Kyoto and Sprague-Dawley rats) were fed high- or basal NaCl diets. After 2.

Altered stores of atrial natriuretic peptide in specific brain nuclei of NaCl-sensitive spontaneously hypertensive rats.

Previous studies from our laboratories have demonstrated a selective increase in stores of atrial natriuretic peptide (ANP) in the anterior hypothalamus of NaCl-sensitive spontaneously hypertensive rats (SHR-S) compared to NaCl-resistant Wistar-Kyoto (WKY) controls and have suggested that anterior hypothalamic ANP contributes to the pathogenesis of NaCl-sensitive hypertension in SHR-S by local inhibition of norepinephrine release. We have also observed blunting of cardiopulmonary and arterial baroreflex function in SHR-S compared to WKY. In the current study, ANP stores in 12 brain nuclei thought to participate in the pathogenesis of hypertension, including locus coeruleus (LC), A1/C1 area (A1/C1), nucleus tractus solitarii (NTS), medial preoptic nucleus (MPON), suprachiasmatic nucleus (SCN), supraoptic nucleus (SON), anterior hypothalamic area (AHA), paraventricular hypothalamic nucleus (PVN), ventromedial hypothalamic nucleus (VMN), dorsomedial hypothalamic nucleus (DMN), lateral hypothalamic nucleus (LN), and posterior hypothalamic area (PHA), were compared in 10-week-old male SHR-S and WKY rats following 3 weeks of 1% v 8% NaCl feeding.

High NaCl diet enhances arterial baroreceptor reflex in NaCl-sensitive spontaneously hypertensive rats.

Previous studies from our laboratory have shown that arterial baroreceptor reflex control of lumbar sympathetic nerve activity is blunted in the NaCl-sensitive spontaneously hypertensive rat (SHR-S) compared with either the NaCl-resistant spontaneously hypertensive rat (SHR-R) or the normotensive Wistar-Kyoto (WKY) rat. In the current study, the effect of dietary NaCl supplementation on arterial baroreceptor reflex control of lumbar sympathetic nerve activity and heart rate was assessed in SHR-S and control SHR-R and WKY rats. Male SHR-S, SHR-R, and WKY rats were fed diets containing either 1% or 8% NaCl beginning at 7 weeks of age and were studied at age 9-10 weeks.

Alterations in vasopressin mechanisms in captopril-treated spontaneously hypertensive rats.

The effects of lifetime captopril treatment on vasopressin (VP) were assessed in spontaneously hypertensive rats (SHR). Pregnant and nursing dams were treated with oral Captopril (100 mg/kg/day). After weaning, the pups were maintained on Captopril (50/kg/day) for 19-20 wks.

Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections.

Hippocampal area CA1 provides the major cortical output of the hippocampus, but only its projections to the subiculum and lateral septal nucleus are well characterized. The present study reexamines these extrinsic projections by using anterograde and retrograde tracing techniques. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the septal one-third of CA1 label axons and terminals in subicular, postsubicular, retrosplenial, perirhinal, and entorhinal cortices, lateral septal nucleus, and diagonal band of Broca.

Blockade of endogenous anterior hypothalamic atrial natriuretic peptide with monoclonal antibody lowers blood pressure in spontaneously hypertensive rats.

We have previously shown that the atrial natriuretic peptide (ANP) content of the anterior hypothalamic region of NaCl-sensitive spontaneously hypertensive rats (SHR-S) is higher than that of Wistar-Kyoto (WKY) rats. ANP has been shown to inhibit neuronal norepinephrine release and to reduce the excitability of hypothalamic neurons. This study tested the hypothesis that blockade of endogenous ANP in the anterior hypothalamus by local microinjection of a monoclonal antibody to ANP (MAb KY-ANP-II) lowers blood pressure in SHR-S.

Connections of the retrosplenial granular a cortex in the rat.

Although the retrosplenial granular a cortex (Rga) is situated in a critical position between the hippocampal formation and the neocortex, few studies have examined its connections. The present experiments use both retrograde and anterograde tracing techniques to characterize the afferent and efferent connections of Rga. Cortical projections to Rga originate in the ipsilateral area infraradiata, the retrosplenial agranular and granular b cortices, the ventral subiculum, and the contralateral Rga.

The postsubicular cortex in the rat: characterization of the fourth region of the subicular cortex and its connections.

The hippocampal formation contributes importantly to many cognitive functions, and therefore has been a focus of intense anatomical and physiological research. Most of this research has focused on the hippocampus proper and the fascia dentata, and much less attention has been given to the subicular cortex, the origin of most extrinsic projections from the hippocampal formation. The present experiments demonstrate that the postsubiculum is a distinct area of the subicular cortex.

Dietary Ca2+ increases natriuretic and diuretic responses to volume loading in NaCl-sensitive spontaneously hypertensive rats.

The present study tests the hypothesis that dietary Ca2+ supplementation increases acute diuretic and natriuretic responses to volume loading in the NaCl-sensitive spontaneously hypertensive rat (SHR-S). Seven week old male SHR-S and normotensive Wistar-Kyoto rats (WKY) were fed one of the following diets for 2.5 weeks: basal (0.

Lesions of the anterior hypothalamic area increase arterial pressure in NaCl-sensitive spontaneously hypertensive rats.

In NaCl-sensitive spontaneously hypertensive rats, diets high in NaCl increase arterial pressure and peripheral sympathetic nervous system activity and decrease the sympatho-inhibition mediated by the anterior hypothalamic area. To test the importance of the defect in anterior hypothalamic area-mediated sympatho-inhibition in the pathogenesis of NaCl-sensitive hypertension, bilateral ibotenic acid lesions of the anterior hypothalamic area were made in NaCl-sensitive spontaneous hypertensive rats, in NaCl-resistant spontaneously hypertensive rats and in normotensive, NaCl-resistant Wistar Kyoto rats. In NaCl-sensitive spontaneous hypertensive rats on a basal NaCl diet, the anterior hypothalamic area lesions caused a rapid rise in arterial pressure within the first week after surgery; by 21 days after surgery, mean systolic arterial pressure of the lesion group was 24 mmHg higher than that of the sham-operated group.

Dietary Ca2+ prevents NaCl-sensitive hypertension in spontaneously hypertensive rats by a sympatholytic mechanism.

The current study tested the hypothesis that dietary Ca2+ supplementation reverses the NaCl-sensitive component of hypertension and the associated neurochemical abnormalities in the NaCl-sensitive spontaneously hypertensive rat (SHR-S). Male SHR-S were begun on one of four diets at 8 weeks of age: control (0.75% NaCl/0.

NaCl does not affect hypothalamic noradrenergic input in deoxycorticosterone acetate/NaCl and Dahl salt-sensitive rats.

Previous studies from our laboratories demonstrated that dietary NaCl supplementation in NaCl-sensitive spontaneously hypertensive rats elevates blood pressure, increases peripheral sympathetic nervous system activity, and depresses endogenous norepinephrine stores and turnover in the anterior hypothalamus. These findings suggest that reduced noradrenergic input to sympathoinhibitory neurons in anterior hypothalamus contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. The current study tested the hypothesis that dietary NaCl supplementation depresses endogenous norepinephrine stores and turnover in anterior hypothalamus of two other NaCl-sensitive models of hypertension, the Dahl salt-sensitive rat and the deoxycorticosterone acetate/NaCl hypertensive rat, thus increasing blood pressure by reducing noradrenergic input to the anterior hypothalamus.

The connections of presubiculum and parasubiculum in the rat.

The present study describes the differences and similarities between the connections of the presubiculum and parasubiculum based on retrograde and anterograde tracing experiments. The results demonstrate that both areas have several similar afferent connections, particularly those from subcortical areas such as the claustrum, diagonal band of Broca, anterior thalamus, nucleus reuniens, locus coeruleus, and raphe nuclei. Both subicular areas also are innervated by axons originating in the ipsilateral and contralateral entorhinal cortex, presubiculum, and parasubiculum.

Dendritic bundling in layer I of granular retrosplenial cortex: intracellular labeling and selectivity of innervation.

The extrinsic projections to and from the retrosplenial cortex have been studied in detail, but the intrinsic circuitry within this region has been characterized less completely. To further define the internal connections, small injections of the retrograde, fluorescent tracer Fluorogold were made into the retrosplenial cortex of the rat. These injections label neurons in layers II-V of the contralateral homotopic cortex.

Changes in cerebrospinal fluid Na+ concentration do not underlie hypertensive responses to dietary NaCl in spontaneously hypertensive rats.

This study tests the hypothesis that dietary NaCl loading increases cerebrospinal fluid (CSF) Na+ concentration in NaCl-sensitive spontaneously hypertensive rats (SHR-S), resulting in an increase in arterial pressure. The high NaCl diet caused a significant rise in systolic arterial pressure in SHR-S but not in normotensive Wistar Kyoto (WKY) rats. In contrast, the high NaCl diet caused a transient rise in CSF Na+ that was similar in amplitude in SHR-S and WKY.

Dopamine D2 receptors in the posterior region of the nucleus tractus solitarius mediate the central pressor action of quinpirole (LY171555).

Our previous studies demonstrated that intravenous (IV) administration of the selective dopamine (DA) D2 receptor agonist quinpirole (LY171555) induces a pressor response in conscious Sprague-Dawley (S-D) rats through a central mechanism. The present study was designed to identify the neurons which medicate this pressor response. Injection of quinpirole (1-150 micrograms/kg) into the 4th ventricle produced a greater pressor response of a more rapid onset than similar injections into the lateral ventricle in conscious, freely moving S-D rats, suggesting a site of action in brainstem.

Impaired reflex response to volume expansion in NaCl-sensitive spontaneously hypertensive rats.

Abnormal baroreceptor reflex function that antedates or is a consequence of NaCl loading could contribute to the NaCl-induced exacerbation of hypertension in NaCl-sensitive spontaneously hypertensive rats (SHR-S). The current study tested the hypothesis that an impairment in cardiopulmonary baroreceptor reflex function exists in SHR-S before NaCl loading. The reflex response to volume expansion was compared in SHR-S, NaCl-resistant SHR (SHR-R), and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats maintained on a normal NaCl diet.

Dietary Ca2+ prevents NaCl-induced exacerbation of hypertension and increases hypothalamic norepinephrine turnover in spontaneously hypertensive rats.

Dietary calcium (Ca2+) supplementation lowers blood pressure in many forms of genetically mediated and experimentally induced hypertension. The present study tested the hypothesis that neuronal mechanisms underlie the blood pressure-lowering effect of dietary Ca2+ in NaCl-sensitive spontaneously hypertensive rats (SHR-S). SHR-S were fed one of the following diets: control (0.

High NaCl diets increase alpha 2-adrenoceptors in renal cortex and medulla of NaCl-sensitive spontaneously hypertensive rats.

Diets high in NaCl simultaneously elevate renal alpha 2-adrenoceptor binding and exacerbate hypertension in young NaCl-sensitive spontaneously hypertensive rats (SHR-S). The present study tests the hypothesis that in SHR-S on a high NaCl diet, an upregulation of renal alpha 2-adrenoceptors is present in densely innervated areas of the kidney, and this precedes the increase in blood pressure. Seven week old SHR-S fed on a high (8%) compared to basal (1%) NaCl diet for 2 weeks displayed significantly exacerbated hypertension and elevated renal alpha 2-adrenoceptor binding in both cortex and medulla.

Renal nerve contribution to NaCl-exacerbated hypertension in spontaneously hypertensive rats.

Previous studies demonstrate that bilateral renal denervation enhances urinary sodium excretion and delays the onset of hypertension in young (7-week-old) spontaneously hypertensive rats (SHR) maintained on ordinary laboratory chow. We interpret these data as suggesting that increased renal nerve activity in this model contributes to hypertension by causing excess sodium retention. More recent studies show that dietary NaCl supplementation increases blood pressure and peripheral sympathetic nervous system activity in NaCl-sensitive SHR (SHR-S).