Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats

The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to ‘mental stress’ in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during ‘rest’ and during a 20 min period of ‘mental stress’. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64±5%) than in WKY (-34±7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during ‘mental stress’ the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e. g. the renal and splanchnic regions during increased alertness.     

Renal dopamine and noradrenaline excretion during CNS-induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS-induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS-induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS-induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS-induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS-induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

Renal dopamine and noradrenaline excretion during CNS‐induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS‐induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS‐induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS‐induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS‐induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS‐induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

Renal sodium excretion after oral or intravenous sodium loading in sodium-deprived normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg^-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY.     

Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats

This study examined age-related changes in renal dopaminergic activity and expression of amino acid transporters potentially involved in renal tubular uptake of l-DOPA in Wistar Kyoto (WKY) and spontaneously hypertensive rats. Aging (from 13 to 91 weeks) was accompanied by increases in systolic blood pressure (SBP) in both WKY and SHR. The sum of urinary dopamine and DOPAC and the urinary dopamine/l-DOPA ratio were increased in aged SHR but not in aged WKY. The urinary dopamine/renal delivery of l-DOPA ratio was increased in both rat strains with aging. LAT2 abundance was increased in aged WKY and SHR. The expression of 4F2hc was markedly elevated in aged SHR but not in aged WKY. ASCT2 was upregulated in both aged WKY and SHR. Plasma aldosterone levels and urinary noradrenaline levels were increased in aged WKY and SHR though levels of both entities were more elevated in aged SHR. Activation of the renal dopaminergic system is more pronounced in aged SHR than in aged WKY and is associated with an upregulation of renal cortical ASCT2 in WKY and of LAT2/4F2hc and ASCT2 in SHR. This activation may be the consequence of a counter-regulatory mechanism for stimuli leading to sodium reabsorption.     

The renal kallikrein-kinin system in spontaneously hypertensive rats

In male spontaneously hypertensive rats (SHRSP) of the stroke prone strain (Okamoto) and in normotensive Wistar-Kyoto rats (WKY) urinary kallikrein excretion was investigated at different age and at drug-induced diuresis.In rats of both strains from 7th till 19th week of age urinary kallikrein excretion increased with age. In SHRSP of 7th till 11th week of age kallikrein excretion was higher than in WKY rats, while it was lower in the 48-week-old SHRSP. No correlation was found between urinary kallikrein excretion and systolic blood pressure.In SHRSP and WKY rats a similar daily rhythm of kallikrein excretion in urine was found being high in the early morning and low in the afternoon. Kallikrein excretion correlated significantly with urine volume.The loop diuretic bumetanide (4 and 40 mg/kg) induced diuresis and natriuresis in both strains, however more marked in the WKY rats than in the SHRSP. Urinary kallikrein excretion, however, showed in both strains the same biphasic course with a short lasting increase and a secondary decrease. Thus, in the average urinary kallikrein excretion was not effected by the drug.Prolonged treatment with furosemide over 5 days (125 mg/kg) resulted in an increase in kallikrein excretion in urine, more pronounced in the WKY rats than in the SHRSP.The observed results suggest that renal kallikrein-kinin system is not involved in the development of spontaneous hypertension as a pathogenetic factor, but rather is influenced by other factors like hormone interactions, i.e. mineralocorticoids and catecholamines, as well as renal function and acute changes in urine flow.Herrn Professor Dr. med. W. Kaufmann zum 60. Geburtstag     

Acute Immune and Non-Immune Inflammatory Response in Spontaneously Hypertensive Rats and Normotensive Rats. Role of Endogenous Nitric Oxide

Summary The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated. Results The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR. Conclusion The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.     

Influence of neonatal handling on blood pressure,locomotor activity,and preweanling heart rate in spontaneously hypertensive and Wistar Kyoto rats

This experiment tested the hypothesis that increased stimulation early in development would (a) alter developmental changes in heart rate and behavioral reactivity and (b) affect the level at which blood pressure was regulated in adulthood. For this purpose, the effects of daily handling and maternal separation (3 min per day) on both behavioral and cardiovascular measures were examined in spontaneously hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) rats. Prior to weaning, elevated heart rates in pups handled during the first postnatal week were most pronounced among 4-week-old prehypertensive SHR pups. Early handling affected behavior observed during openfield testing similarly in young adult rats of the SHR and WKY strains (e.g., increased locomotor activity on the first day of testing). In female rats of the WKY strain, early handling resulted in a lower baseline blood pressure; the blood pressure; the blood pressure of SHR rats was not affected by increased stimulation in infancy. Examination of longitudinal data yielded no support for a direct association between behavioral reactivity or preweaning heart rate and high blood pressure. These findings demonstrate the influence of both early environmental conditions and genetic factors on maturation within the cardiovascular system and suggest that genetic models of pathological conditions may provide a productive means of examining environmentally shaped aspects of individual differences in physiological regulation.     

Improvement of organ damage by a non-depressor dose of imidapril in diabetic spontaneously hypertensive rats

Many clinical trials have demonstrated that angiotensin converting enzyme inhibitors have protective effects on organ damage, suggesting the importance of inhibition of the renin-angiotensin system. In this study, we investigated the effects of a non-depressor dose of imidapril on organ damage induced by diabetes and hypertension. Diabetes was induced by an intravenous injection of streptozotocin (STZ, 40 mg/kg) in 15-week-old male spontaneously hypertensive rats (SHR). Imidapril (2 mg/kg/day) or vehicle was given orally for 28 days, and then the heart weight, left ventricle mass (LVM), urinary albumin excretion (UAE) and endothelial function were examined, as well as the urinary NOx level and local hepatocyte growth factor (HGF) expression. There were no significant differences between the treated groups in systolic blood pressure and plasma parameters. On the other hand, UAE was significantly suppressed in the imidapril-treated group (450+/-44 mg/day) compared to the vehicle-treated group (963+/-182 mg/day) (p<0.01). Moreover, endothelial function assessed by dilative reaction to acetylcholine as well as cardiac hypertrophy assessed by both heart/body weight ratio and LVM were significantly improved in the imidapril-treated group (p<0.05 and p<0.01, respectively). The urinary NOx concentration and local HGF expression in vessel walls were also significantly increased in the imidapril-treated group (p<0.01). A non-depressor dose of imidapril showed protective effects against organ damage in diabetic SHR, which may be partially due to the increase of HGF and NO.     

Sensitivity of pressor responses to central hypertonic saline is greatly enhanced even in pre-hypertensive spontaneously hypertensive rats

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR. The basal mean blood pressure was almost the same in 4-week-old SHR and age-matched Wistar Kyoto rats (WKY), whereas it was greater in 15-16-week-old SHR than in age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 230 mM NaCl) produced an increase in blood pressure in both 4-week-old and 15-16-week-old SHR, whereas it did not affect blood pressure in both age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 260 mM NaCl) produced an increase in blood pressure in all rats but the pressor response was greater in both 4-week-old and 15-16-week-old SHR than in respective age-matched WKY. Intracerebroventricular injection of Phe-Met-Arg-Phe amide (FMRF), an FMRF-inducible sodium channel activator, produced an increase in blood pressure in all rats but the pressor response was greater in SHR than in WKY at both ages. These findings indicate that the sensitivities of pressor responses to intracerebroventricular hypertonic saline and FMRF are enhanced not only in hypertensive but also in pre-hypertensive SHR.     

TGF-mediated oscillations in the proximal intratubular pressure: differences between spontaneously hypertensive rats and Wistar-Kyoto rats

A highly sensitive oscillatory tubulo-glomerular feedback (TGF) response has previously been demonstrated in normotensive Sprague-Dawley rats. The purpose of the present study was to examine whether such as oscillating TGF-response could be elicited in Wistar-Kyoto rats (WKY) and genetically hypertensive rats (SHR) and furthermore if any differences in the TGF-response characteristics between SHR and WKY rats could be detected. The closed loop function of the TGF-system was studied. In 12-18-week-old WKY rats regular oscillations in the intratubular pressure occurred spontaneously. The median frequency were 29.7 mHz (range 20-46.7 mHz). In SHR rats, spontaneous oscillations also occurred, but these were highly irregular. Spontaneous oscillations were more frequent in WKY than in SHR (88% vs. 54%). In both strains, oscillations could be elicited by free flow microperfusion with artificial tubular fluid (ATF). When furosemide was added to the ATF in a concentration of 0.1 mM, the oscillations were abolished in both strains of rats. It is concluded that, in both strains of rats the oscillatory phenomena depend upon TGF activity. It is suggested that the irregular pattern of the oscillations observed only in SHR rats may represent a chaotic process.     

Methylphenidate normalizes elevated dopamine transporter densities in an animal model of the attention-deficit/hyperactivity disorder combined type,but not to the same extent in one of the attention-deficit/hyperactivity disorder inattentive type

The spontaneously hypertensive rat (SHR/NCrl) is a validated model of attention-deficit/hyperactivity disorder (ADHD) combined subtype, whereas a recently identified substrain of the Wistar Kyoto rat (WKY/NCrl) is a model of ADHD inattentive subtype. In this study, we first examined the expression of genes involved in dopamine signaling and metabolism in the dorsal striatum and ventral mesencephalon of these two rat strains, as well as three reference control strains (WKY/NHsd, WK/HanTac, and SD/NTac) using quantitative real time RT-PCR. Next, striatal dopamine transporter (DAT) density was determined by ligand binding assay in the two ADHD-like strains at different developmental stages and after methylphenidate treatment. In adult rats, the mRNA expression of DAT and tyrosine hydroxylase was elevated in SHR/NCrl and WKY/NCrl rats compared to control strains, with differences between SHR/NCrl and WKY/NCrl rats also evident. During normal development, changes of striatal DAT densities occurred in both strains with lower densities in WKY/NCrl compared to SHR/NCrl after day 25. Two-weeks methylphenidate treatment during different developmental stages was associated with decreased striatal DAT density in both rat strains compared to the non-treated rats with more pronounced effects followed prepubertal treatment. These results suggest differences in the pathophysiology of the combined versus the predominantly inattentive animal model of ADHD. Finally, treatment with methylphenidate might reduce elevated DAT levels more effectively in the combined subtype especially when applied before puberty.     

No aggravation of the course of experimental glomerulonephritis in spontaneously hypertensive rats.

Functional and morphologic glomerular alterations induced by antiglomerular basement membrane (anti-GBM) nephritis were investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto controls (WKY) for assessment of the role of systemic hypertension in immunologically mediated renal injury. Over a 6-week period serial measurements of systolic blood pressure (BP), serum creatinine (SCreat), creatinine clearance (CCreat), and urinary albumin excretion (UAlbV) were obtained with inulin clearances (CInulin) at the end of the study. Renal tissue was examined by light microscopy (LM), electron microscopy, immunofluorescence, flash 3H-thymidine autoradiography (AR), and staining for nonspecific esterase (NSE). Immunologic humoral response was evaluated by measurement of rat anti-rabbit IgG antibody production. At all time periods studied, SHR and WKY rats with anti-GBM nephritis demonstrated comparable elevations in SCreat and UAlb V as well as diminution of CCreat and CInulin as compared with non-nephritic control rats of each strain. In nephritic WKY rats mild hypertension developed, whereas in nephritic and control SHR rats marked elevations in BP developed. Morphologic injury as assessed by percent glomerular crescents and hypercellularity on LM, numbers of monocyte macrophages by NSE staining, immunofluorescence for IgG, C3, fibrinogen and Ia positivity, and numbers of glomerular 3H-thymidine-labeled cells by AR was notably comparable in both nephritic strains. Humoral antibody responses were also shown to be similar in all rats studied. These results demonstrate that the 5-week course of experimental anti-GBM nephritis is not exacerbated by systemic hypertension. Glomerular autoregulatory capacity may be important in determining the extent of immune-mediated renal injury.     

Renal and cardiovascular effects of atrial natriuretic peptide in Wistar-Kyoto and spontaneously hypertensive rats during a chronic salt loading

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were maintained on tap water or 1.5% NaCl for 3 weeks. During the high sodium regime 24-h urinary sodium excretion increased 10-fold and the basal blood pressure increased in the SHR. After 3 weeks the rats received arterial (carotid artery), venous and bladder catheters (suprapubic). Saline was infused continuously and in conscious rats atrial natriuretic peptide (alpha-hANP) was administered as bolus injections (8 and 16 nmol kg-1) and the blood pressure and heart rate and the urinary excretions of sodium, potassium (flame photometry), noradrenaline and dopamine (HPLC) were followed at 5-min intervals. The administration of ANP caused a short-lasting blood pressure reduction, tachycardia, diuresis and increased urinary excretions of sodium, potassium, noradrenaline and dopamine. The blood pressure responses to ANP did not differ between the rat strains, irrespective of the diet. The natriuresis and diuresis to ANP was reduced in animals on a high sodium diet, especially in the SHR. This may be interpreted as a down-regulation of target organ responsiveness to ANP during a high sodium diet and the inappropriately large decrease in the responsiveness that was observed in the SHR may be related to increase in blood pressure during the high sodium diet.     

The effects of enalapril on the natriuretic response evoked by an oral sodium load in sodium deprived normotensive and hypertensive rats

Previous studies have shown that an oral sodium load during sodium deprivation is excreted faster than an intravenous load. We wanted to study whether the renin-angiotensin-aldosterone system might be associated with this phenomenon and therefore the influence of the angiotensin converting enzyme (ACE) inhibitor enalapril was investigated. The experiments were performed on four strains of rat: spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, inbred hypertension-prone (SS/Jr) and hypertension-resistant (SR/Jr) Dahl rats. In SHR and WKY rats pretreated with enalapril it was observed that an intravenous sodium load induced a renal sodium excretion which was between two and five times larger than that seen after an oral load. In SR/Jr and SS/Jr rats the sodium excretion was the same regardless of the route of administration. In SS/Jr rats sodium excretion increased three- to fourfold upon sodium repletion, whereas no significant increase was observed in SR/Jr rats. Thus, the present results indicate that an intact renin-angiotensin system is necessary for the interplay between the gastrointestinal tract and kidney.     

Renal dysfunction after chronic blockade of nitric oxide synthesis

The effects of the chronic inhibition of nitric oxide (NO) on renal hemodynamics and tubular function were studied in rats treated for 8 weeks with the NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg/day). In addition, the effect of L-NAME administration on vasoactive systems (renin-angiotensin system, aldosterone, catecholamines, endothelin, and thromboxane A(2)) was evaluated. Chronic inhibition of NO significantly elevated blood pressure, reduced glomerular filtration rate and renal blood flow, blunted the pressure-diuresis-natriuresis response, and increased protein urine excretion. All these changes were associated with blunted nitrite production in response to acetylcholine in glomeruli. No changes were observed in the plasma levels of either renin activity, aldosterone, or endothelin in L-NAME-treated rats. Similarly, no differences were observed in the urinary excretion of thromboxane B(2) between both group of animals. By contrast, plasma concentrations of both epinephrine and norepinephrine were elevated in rats treated with L-NAME. In summary, the results show that chronic blockade of NO produced not only alterations in renal function, but also renal damage, suggesting an important renoprotective role of NO. An activation of sympathoadrenal system could participate in these renal alterations.     

Central nitric oxide blocks vasopressin, oxytocin and atrial natriuretic peptide release and antidiuretic and natriuretic responses induced by central angiotensin II in conscious rats

The presence of nitric oxide synthase (NOS), the enzyme that catalyses the formation of nitric oxide (NO), in the circumventricular organs and magnocellular neurones suggests an important role of NO in the modulation of vasopressin (AVP) and oxytocin (OT) release. Intracerebroventricular (I.C.V.) injection of angiotensin II (Ang II) stimulates the release of AVP, OT and atrial natriuretic peptide (ANP), with the resultant antidiuretic and natriuretic effects. This study investigated the interaction between nitrergic and angiotensinergic pathways on the release of AVP, OT and ANP and on urinary volume and sodium excretion in water-loaded rats. Unanaesthetized, freely moving, male Wistar rats received two water loads followed by an injection into the lateral ventricle of an inhibitor of NOS (L-NAME), a NO donor [3-morpholinylsydnoneimine chloride (SIN-1) or S-nitroso-N-acetyl penicillamine (SNAP)] or vehicle (isotonic saline) and, 20 min after, they received a second I.C.V. injection of Ang II or vehicle. Injections of L-NAME or Ang II produced an increase in plasma levels of AVP, OT and ANP, a reduction in urinary volume and an increase in sodium excretion. Pretreatment with L-NAME enhanced the Ang II-induced increase in AVP, OT and ANP release, as well as the antidiuresis and natriuresis. Injection of SIN-1 or SNAP did not modify hormonal plasma levels and urinary parameters. In contrast SNAP blocked the AVP, OT and ANP release, as well as antidiuretic and natriuretic responses induced by ANG-II. Thus, the central nitrergic system can act to inhibit AVP, OT and ANP secretion and the antidiuretic and natriuretic effects in response to Ang II.     

Cardiovascular concomitants of tactile and acoustic startle responses in spontaneously hypertensive and normotensive rats

In the present study we have simultaneously investigated cardiovascular and behavioral responses to repeated tactile and acoustic stimulation in adult, male, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Blood pressure and heart rate responses were increased in SHR vs. WKY rats following both types of stimuli. The pressor responses, but not the tachycardic responses, habituated with repeated stimulation in both strains and with both stimulus modalities. The rates of habituation were not significantly different between the two strains. Magnitudes of the behavioral startle responses were significantly elevated in SHR vs. WKY rats with tactile, but not with acoustic stimulation. No significant differences were found between the two strains with respect to the latency, with which the startle responses occurred. These data indicate that SHR as compared to WKY rats respond to repeated stimulation with two different stimulus modalities (tactile and acoustic) with significantly increased pressor and tachycardic responses. This cardiovascular hyperreactivity is not due to different degrees of habituation between the two strains and can be observed even in the absence of significant differences in standard behavioral startle response measures.     

Adrenal α2-adrenergic receptors in the aging normotensive and spontaneously hypertensive rat

This study investigates α₂-adrenergic receptor (α₂AR) mediated feedback inhibition of catecholamine release from the adrenal medulla of adult (52 weeks) and old (98 weeks) spontaneously hypertensive rats (SHR) and normotensive controls Wistar Kyoto (WKY) rats. Adrenal epinephrine content as well as the spontaneous and the nicotinic-evoked release of epinephrine were similar between adult SHR and WKY rats. Aging produced a significant reduction in epinephrine synthesis in WKY rats. In contrast, in SHR aging produced a significant increase in epinephrine release without significant changes in epinephrine synthesis. The α₂AR agonist medetomidine abolished (80–90% inhibition) the nicotinic-evoked release of epinephrine in adult SHR and WKY rats. With aging, this effect was unaltered in WKY rats but was significantly decreased in SHR (30% inhibition). Adrenal α_2AAR mRNA levels were significantly reduced in old SHR compared with age matched WKY rats. In conclusion, in aging the α₂AR mediated feedback inhibition of epinephrine release from the adrenal medulla is preserved in WKY rats but compromised in SHR, resulting in increased epinephrine release.     

Aging effects on elevated plus maze behavior in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male and female rats

Male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were assessed at one of two ages (postnatal day 74 or 346) for open field locomotor activity and anxiety-related behavior in the elevated plus maze (EPM). In general, the SHR displayed the least anxiety-related behavior, an effect that was magnified with age. At 11 months of age, the SHR more frequently entered and remained longer in the open arms than either the SD or the WKY strains. EPM behavior of the WKY strain was much less affected by age than that of the SD strain which displayed increased anxiety-related behavior with age. At the younger age, the typical sex effects were apparent; specifically, females exhibited a shorter duration in the closed arms. While the SHR were the most active strain in the EPM at both ages, they were more active in the open field only at the older age. In general, age-related changes in open field activity mirrored those of the EPM. These results provide a more comprehensive illustration of aging-related behavioral changes in male and female SHR, WKY and SD rats.