Hypertension In SHR Research Articles

Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure.

It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model. Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons. There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups. The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.

The Effects of Coadministration of Morphine and Naloxone on the Severity of Hypertension in SHR During Experimental Inflammation

The Effects of Coadministration of Morphine and Naloxone on the Severity of Hypertension in SHR During Experimental Inflammation

Difference in topology and numbers of barosensitive catecholaminergic and cholinergic neurons in the medulla between SHR and WKY rats

We hypothesized that there may be a significant difference in the neuronal composition of the baroreceptor reflex pathway between normotensive Wistar Kyoto (WKY) and spontaneously hypertensive SHR rats. Using the double-immunoreactive (IR) method, the topology and numbers of barosensitive neurons that contain glutamate (Glu), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT) and choline acetyltransferase (ChAT) were compared between the two strains. The control rats were sham-operated only for cannulation of the trachea and femoral artery/vein. The test rats were injected with the pressor agent phenylephrine to raise blood pressure and stimulate arterial baroreceptors. In both the control and test experiments, the c-Fos/Glu-, GAD-, TH- and PNMT-IR neurons were found in the nucleus tractus solitarii (NTS) and ventrolateral medulla (VLM), while the FosB/ChAT-IR neurons were found in the NTS, dorsal motor nucleus of the vagus (DMX) and nucleus ambiguus (AMB). In the control experiment, no significant difference in numbers was recognized in any of the double-IR neurons between the two strains. In the test experiment, the numbers of FosB/ChAT-IR neurons in the NTS, DMX and AMB were significantly smaller in SHR than in WKY. The numbers of c-Fos/TH-IR neurons in the caudal VLM were significantly larger in SHR than in WKY. These results suggest that a smaller number of barosensitive cholinergic neurons in the DMX and AMB in SHR causes the weaker baroreceptor-cardiac vagal reflex in SHR, and that a larger number of barosensitive catecholaminergic neurons in the caudal VLM in SHR are involved in the stronger baroreceptor-vasopressin reflex in SHR.

Enhanced Activation of the Mineralocorticoid Receptor in Genetically Hypertensive Rats

The relative abundance and availability of the mineralocorticoid receptor (MCR) appeared to be similar in the heart, kidney and ocular tissues of the genetically hypertensive SHR and normotensive WKY rats by a number of criteria including Western blotting, immunoprecipitation, dot blot analysis, and immunohistochemistry. On the other hand, the activation of the MCR, as judged by binding to DNA cellulose, was significantly enhanced in the hearts and kidneys of 14 week-old, hypertensive, SHR rats compared to the normotensive WKY animals. The activation of the renal MCR was elevated in the SHR strain even at the age of six weeks when the tail arterial pressure was statistically identical to that of the WKY strain. Thus, precocious receptor activation may represent a primary lesion leading to hypertension in the SHR strain, thereby providing a new model to elucidate the hypertensive state.

Metabolic features of newly established congenic diabetes-prone BB.SHR rat strains

The well-known association of hypertension and diabetes mellitus and the lack of suitable animal models to study diabetic hypertension prompted us to transfer 4 chromosomal regions with quantitative trait loci (QTLs) for blood pressure of the spontaneously hypertensive SHR rat onto the genetic background of the diabetes-prone and normotensive BB/OK rat. Four congenic strains developed are named as BB.Sa (Chr. 1), BB.Bp2 (Chr. 18), BB.1K (Chr.20) and BB.Xs (Chr.X). Because the systolic blood pressure is significantly elevated in all congenics, renal related traits were investigated in serum and urine. Comparing BB/OK and their congenic derivatives, significant differences were found in all serum and in 7 out of 8 urine constituents studied. Most significant differences were found between BB/OK and BB.Bp2 rats. Significant differences were also found between the different congenic strains indicating that each congenic strain has its own phenotype and that each chromosomal region contains most probably further QTLs for some of the traits studied.

Effects of Naloxone Hydrochloride and Naloxone Methiodide on the Development and Severity of Hypertension in SHR During Experimental Inflammation

Effects of Naloxone Hydrochloride and Naloxone Methiodide on the Development and Severity of Hypertension in SHR During Experimental Inflammation

Endothelium-dependent vasodilation in the uvea of hypertensive and normotensive rats

PURPOSE. The effects of endothelium-related substances such as acetylcholine, a stimulator of endogenous NO-production, the NO-synthesis inhibitor L-NMMA, the exogenous NO-donor sodium nitroprusside and the endothelin (ET) A -receptor antagonist BQ123, on uveal blood flow were investigated in normotensive and hypertensive SHR rats. METHOD. The radioactively-labelled microsphere method was applied for the measurement of regional blood flow in the uvea. RESULTS. Under resting conditions, local blood flow was lower in the hypertensive animals. The increase in choroidal blood flow (145 ± 50%; P < 0.01) and reduction in vascular resistance (-58 ± 7%; P < 0.01) observed in the WKY after IV infusion of acetylcholine, 2 µg × kg bw -1 × min -1, were significantly less pronounced in animals pretreated with L-NMMA, indicating local formation of NO as a vasodilator mechanism. In contrast, acetylcholine did not induce significant vasodilation in the choroid of SHR rats. In the anterior uvea of both strains, acetylcholine did not affect local blood flow. L-NMMA, 20 mg × kg bw -1, alone reduced blood flow in the entire uvea of both strains. Intravenous injection of BQ123, 1 mg × kg bw -1, did not affect regional blood flow in the uvea of WKY or SHR animals. Infusion of acetylcholine following ET A -receptor blockade induced vasodilation in both the choroid and anterior uvea in the WKY but not in the SHR. CONCLUSIONS. Acetylcholine-stimulated NO-mediated vasodilation, but not basal NO-formation, was impaired in the choroid of the SHR. Furthermore, an interaction between vasoconstricting ET and acetylcholine was found in the anterior uvea of normotensive but not hypertensive rats.

Reduction of insulin resistance attenuates the development of hypertension in sucrose-fed SHR

We examined the effect of pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, on the development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old male SHR received 12% sucrose dissolved in tap water as drinking water. For 5 weeks, half of the rats were given regular rat chow, and the rest were fed with rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma insulin levels were examined before and after oral glucose administration by gavage. Sucrose treatment elicited a significant elevation of systolic blood pressure 3 weeks after the beginning of treatment; pioglitazone treatment attenuated this elevation. The insulin resistance and hyperinsulinemia observed in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone treatment also significantly reduced the urinary excretion of catecholamines and plasma renin activity, both of which were significantly greater in sucrose-fed SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone treatment also attenuated the development of hypertension in SHR fed the regular rat chow, but not in WKY rats. These results indicate that insulin resistance and hyperinsulinemia play an important role in the development of hypertension in SHR probably through the activation of the renin-angiotensin system and sympathetic nervous outflow. This study also shows that chronic sucrose treatment exacerbated the development of hypertension through these mechanisms, precipitating insulin resistance.

Hyperinsulinemia Induces Myocardial Infarctions and Arteriolar Medial Hypertrophy in Spontaneously Hypertensive Rats

To investigate the effects of hyperinsulinemia on the myocardial vessels, long acting insulin (mixtard, a combination of 30% regular human insulin and 70% NPH human insulin) was injected daily for 8 weeks, intraperitoneally, in two strains of rats, normotensive WKY and hypertensive SHR. There were four groups in all, a control group, and an insulin-injected group in each strain. The drinking water contained 10% glucose to prevent hypoglycemia in the insulin-injected rats. At the end of the 8 weeks experimental period, after measuring blood pressure and taking blood for the determination of glucose, urea, creatinine, and insulin, the rats were killed. The organs were fixed in formaldehyde. The blood glucose levels were higher at the end of the experiment, in both the placebo-(saline)-injected and the insulin-injected rats. Blood pressure rose significantly only in the insulin-injected SHR. The intramyocardial arterioles in the insulin-injected SHR had a significantly thicker vascular wall than the placebo-injected SHR, as represented by the vessel wall to lumen ratio, because of hypertrophy of the media. When compared with the placebo injected WKY rats, there was a higher wall/lumen ratio of the intramyocardial arterioles in the insulin-injected WKY, but the difference did not reach significance. Heart weights factored by body weights was significantly higher in insulin-injected as compared with placebo-injected SHR. Myocardial infarctions were observed in four of eight rats in the insulin-injected SHR group despite the fact that there were no signs of atherosclerosis or intimal thickening. It is possible that the increase in heart weight and the probable increase in metabolic activity resulting from hyperinsulinemia, together with the increased oxygen demand of the myocardium and the arteriolar narrowing, may have contributed to the occurence of myocardial infarctions in the absence of atherosclerotic coronary occlusion.

Elevated 12-lipoxygenase activity in the spontaneously hypertensive rat

We have previously demonstrated that administration of inhibitors of the lipoxygenase (LO) pathway of arachidonic acid metabolism lowers blood pressure in hypertensive rats. In addition, we have shown that LO inhibition attenuates pressor agonist-induced vascular reactivity in vitro and calcium mobilization in cultured vascular smooth muscle cells (VSMC). To further elucidate the relationship between elevated LO activity and hypertension, 4, 8, and 12 week old hypertensive SHR were compared with age-matched Wistar-Kyoto (WKY) rats for plasma 12 (S)-hydroxyeicosatetraenoic acid (12-HETE) concentration. 12-HETE levels were significantly elevated in the SHR compared to the WKY (SHR elevated by 154%, 159%, and 272% compared to WKY at 4, 8, and 12 weeks, respectively, P < .01 for all ages). There were no differences in plasma potassium levels between SHR and WKY at any of the ages tested. Plasma aldosterone levels and plasma renin activity were in the normal range at the three ages. At 12 weeks of age, both serum (4.72 ± 0.23 v 2.18 ± 0.33 μg/mL, P < .01), and aortic smooth muscle 12-HETE levels (0.94 ± 0.09 v 0.66 ± 0.08 μg/mg protein, P < .05) were elevated in SHR compared with WKY. The 12 week old SHR were given a bolus of the LO inhibitor 5,8,11-eicosatriynoic acid (ETI, 7 mg/kg, intravenously) and blood pressure measured after 20 min. ETI reduced mean systolic blood pressure from 175.8 ± 4.2 to 141.6 ± 5.9 mm Hg ( P < .05). To investigate these effects of HETEs, cultured vascular smooth muscle cells were pretreated for 1 min with 12 (S) HETE and then challenged with angiotensin II (AngII). The addition of 12 (S) HETE increased AngII-induced intracellular calcium levels in normal cultured rat vascular smooth muscle cells by 78% compared to vehicle ( P < .05). Thus, LO products, which are high in SHR, may contribute to vascular tone through alterations in the intracellular calcium signal by potentiating calcium responses to pressors such as Ang II.

Elevated 12-Lipoxygenase Activity in the Spontaneously Hypertensive Rat

We have previously demonstrated that administration of inhibitors of the lipoxygenase (LO) pathway of arachidonic acid metabolism lowers blood pressure in hypertensive rats. In addition, we have shown that LO inhibition attenuates pressor agonist-induced vascular reactivity in vitro and calcium mobilization in cultured vascular smooth muscle cells (VSMC). To further elucidate the relationship between elevated LO activity and hypertension, 4, 8, and 12 week old hypertensive SHR were compared with age-matched Wistar-Kyoto (WKY) rats for plasma 12(S)-hydroxyeicosatetraenoic acid (12-HETE) concentration. 12-HETE levels were significantly elevated in the SHR compared to the WKY (SHR elevated by 154%, 159%, and 272% compared to WKY at 4, 8, and 12 weeks, respectively, P < .01 for all ages). There were no differences in plasma potassium levels between SHR and WKY at any of the ages tested. Plasma aldosterone levels and plasma renin activity were in the normal range at the three ages. At 12 weeks of age, both serum (4.72 +/- 0.23 v 2.18 +/- 0.33 microg/mL, P < .01), and aortic smooth muscle 12-HETE levels (0.94 +/- 0.09 v 0.66 +/- 0.08 microg/mg protein, P < .05) were elevated in SHR compared with WKY. The 12 week old SHR were given a bolus of the LO inhibitor 5,8,11-eicosatriynoic acid (ETI, 7 mg/kg, intravenously) and blood pressure measured after 20 min. ETI reduced mean systolic blood pressure from 175.8 +/- 4.2 to 141.6 +/- 5.9 mm Hg (P < .05). To investigate these effects of HETEs, cultured vascular smooth muscle cells were pretreated for 1 min with 12(S)HETE and then challenged with angiotensin II (AngII). The addition of 12(S)HETE increased AngII-induced intracellular calcium levels in normal cultured rat vascular smooth muscle cells by 78% compared to vehicle (P < .05). Thus, LO products, which are high in SHR, may contribute to vascular tone through alterations in the intracellular calcium signal by potentiating calcium responses to pressors such as Ang II.

NEUROBIOLOGY OF l-DOPAergic SYSTEMS

l-DOPA is proposed to be a neurotransmitter and/or neuromodulator in CNS. It is released probably from neurons, which may contain l-DOPA as an end-product, and/or from some compartment other than catecholamine-containing vesicles. The l-DOPA itself produces presynaptic and postsynaptic responses. All are stereoselective and most are antagonized by competitive antagonist. In striatum, l-DOPA is neuromodulator, mother of catecholamines, not only a precursor for dopamine but also a potentiator of children for presynaptic β-adrenoceptors to facilitate dopamine release and postsynaptic D 2 receptors, and ACh release inhibitor. All may cooperate for Parkinson's disease. Meanwhile, supersensitization of increase in l-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or “on-off” during chronic therapy. In lower brainstem, l-DOPA tonically activates postsynaptic depressor sites of NTS and CVLM and pressor sites of RVLM. l-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in NTS. GABA, the inhibitory neuromodulator for baroreflex in NTS, tonically functions to inhibit, via GABA A receptors, l-DOPA release and depressor responses to levodopa. Levodopa inversely releases GABA. l-DOPAergic monosynaptic relay from NTS to CVLM and from PHN to RVLM is suggested. Tonic l-DOPAergic baroreceptor-aortic nerve-NTS-CVLM relay seems to carry baroreflex information. Disturbance of neuronal activity to release l-DOPA in NTS, loss of the activity in CVLM, enhancement of the activity with decreased decarboxylation and increase in sensitivity to levodopa in RVLM may be involved in maintenance of hypertension in SHR. This is a story of “ l-DOPAergic receptors” with extremely high affinity and low density. Copyright © 1996 Elsevier Science Ltd.

Sympathetic nervous system in salt-sensitive and obese hypertension: amelioration of multiple abnormalities by a central sympatholytic agent.

Excess activity of the sympathetic nervous system (SNS) is linked to human obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced SNS activity has been implicated as a contributor to obesity, particularly in animal models, and salt loading usually inhibits SNS activity. We have investigated the relationship between SNS activity, diet, and hypertension in the obese spontaneously hypertensive rat (SHROB), a model with a recessive obesity trait superimposed on a hypertensive background with multiple metabolic abnormalities resembling human syndrome X. We examined the role of SNS overactivity in the adverse impact of excess dietary salt and the possible beneficial effects of sympatholytic therapy. Mean blood pressure (MBP) was increased in SHROB and SHR fed a 4% NaCl diet. The pressor effect of dietary salt was abolished by ganglionic blockade, suggesting that increased SNS activity contributed to the pressor effect of the high-salt diet. Moxonidine, a second-generation central antihypertensive, controlled hypertension in both SHROB and SHR. Kidney damage in SHROB was accelerated by dietary salt and was reduced by moxonidine. Moxonidine elicited progressive weight loss in SHROB but not in SHR. Food intake in SHROB was reduced to the level of lean SHR. SHROB and SHR treated with moxonidine showed improved glucose tolerance. Additionally, SHROB showed reduced levels of triglycerides, cholesterol, and insulin following moxonidine therapy. Inhibition of the SNS, as with moxonidine therapy, may ameliorate multiple abnormalities and have therapeutic advantages in obese hypertensive syndromes.

Improvement of Insulin Resistance Attenuate the Development of Hypertension in SHR

Improvement of Insulin Resistance Attenuate the Development of Hypertension in SHR

Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus.

1. Cardiovascular and renal benefits of a specific angiotensin II (AII) receptor antagonist, losartan (LOS), were assessed in diabetic rats with renal impairment. 2. Uninephrectomized SHR made diabetic by streptozotocin administration were given LOS (5 mg/kg per day, i.p.) alone, captopril (CAP) (50 mg/kg per day, i.p.) alone, or a combination of CAP and LOS via osmotic minipumps for 8 weeks. 3. Both CAP alone and LOS alone completely blocked the development of hypertension in diabetic SHR in the same manner. CAP + LOS did not enhance the antihypertensive effects of LOS alone or CAP alone. 4. CAP + LOS, LOS alone and CAP alone significantly decreased urinary protein excretion and serum creatinine to the same extent. 5. These results indicate that both LOS and CAP exert antihypertensive and renoprotective effects in this model: these actions are mainly through inhibition of AII production.

729-2 Macrophage-Monocyte Invasion is Associated with Greater Cardiac Hypertrophy in Hypertensive Rats

Cardiac hypertrophy is an adaptive response to increased wall stress in hypertension. Although the mechanisms underlying this adaptive response are not clearly understood, a genetic predisposition appears to playa role. We sought to examine the hypothesis that an inflammatory response occurs in the heart early in the course of development of hypertension. We measured blood pressure, heart weight and cardiac macrophage-monocyte invasion in 6 week old SHR and WKY rats with renal hypertension (1 Kidney-1 Clip, 1K1C) or sham-operated controls (SHAM). Macrocyte-monophage invasion was measured as the extent of immunohistochemical staining with ED1, a cytoplasmic antigen in this cell type. Measurements were made at 7 and 21 days post procedure. Renal hypertensive rats, both SHR and WKY, had higher blood pressures at both time points than SHR sham, which in turn had higher blood pressures that WKY sham rats. Heart weight/body weight ratios were highest in SHR-1 K1 C rats, followed by SHR SHAM and WKY 1K1C, and least in WKY sham rats. ED1 staining was also highest in SHR 1K-lC rats, followed by SHR sham rats, and was considerably lower in WKY rats, 1K-1C or sham. Data atthe 21 day time point are shown below: BP (mmHg) Heart wt/body wt (mg/g) ED1 (counts/HPF) SHR 1K1C 205 4.3 20.0 SHR SHAM 170 3.4 15.0 WKY 1K1C 203 3.7 12.5 WKY SHAM 143 2.8 12.5 Thus, significant monocyte-macrophage invasion is a hitherto unrecognized feature of cardiac hypertrophy in SHR rats. We speculate that growth factors released by such cells may contribute to hypertensive cardiac hypertrophy.

Calcium metabolic changes and calbindin-D in experimental hypertension

To examine renal and intestinal calbindin-D in relation to calcium metabolic changes in three different models of experimental hypertension. Spontaneously hypertensive rats (SHR), hypertension-prone Dahl salt-sensitive (Dahl-S) rats and the Goldblatt two-kidney, one clip rat model of renovascular hypertension were examined. Both prehypertensive and hypertensive SHR had significantly lower concentrations of both renal calbindin-D28k and intestinal calbindin-D9k than Wistar control rats. This was accompanied by hypocalcaemia, hypomagnesaemia and increased plasma 1,25(OH)2 vitamin D levels. Induction of hypertension in Dahl-S rats reduced intestinal calbindin-D9k and increased plasma levels of 1,25(OH)2 vitamin D, while renal calbindin-D28k levels, plasma calcium levels and plasma magnesium levels were unchanged. Renovascular hypertension was associated with a significant increase in the intestinal calbindin-D9k, plasma 1,25(OH)2 vitamin D, parathyroid hormone and magnesium levels, while renal calbindin-D2k, plasma calcium and phosphorus levels were unaffected. These three models of experimental hypertension have clearly demonstrated three separate patterns in the regulation of renal and intestinal calbindin-D, which relate to different alterations of factors involved in calcium and magnesium metabolism. In all three models hypertension was accompanied by a significant increase in plasma concentrations of 1,25(OH)2 vitamin D. Only rats with renovascular hypertension showed increased intestinal calbindin-D9k levels, whereas reduced concentrations were found in the SHR and in the hypertensive Dahl-S rats. This indicates the existence of a resistance at the cellular level to 1,25(OH)2 vitamin D affecting the expression of calbindin-D in both SHR and Dahl-S rats.

Antihypertensive effects of BQ-123, a selective endothelin ET A receptor antagonist, in spontaneously hypertensive rats treated with DOCA-salt

We determined the antihypertensive effects of BQ-123 (cyclo(- d-Trp- d-Asp- l-Pro- d-Val- l-Leu-), sodium salt), a selective endothelin ET A receptor antagonist, in spontaneously hypertensive rats treated with deoxycorticosterone acetate-salt (DOCA-salt SHR). BQ-123 (1–30 mg/kg/h) decreased blood pressure in DOCA-salt SHR in a dose-dependent manner, although plasma immunoreactive endothelin-1 did not significantly increase and the maximal contractile response to endothelin-1 in the aorta significantly decreased as compared with values observed in age-matched SHR. These results suggest that endogenous endothelin-1 is involved in the maintenance of hypertension in DOCA-salt SHR, and that circulating endothelin-1 is not sufficient to reflect the physiological role of endothelin-1.

Age and strain differences in rat place learning and hippocampal dentate gyrus frequency-potentiation

Induction of post-tetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from (i) young (6 months old) rats of different strains (Sprague-Dawley, SD; spontaneously hypertensive rats, SHR; and Wistar-Kyoto, WKY), and (ii) from aged (20–24 months old) SD and Fischer 344 (F 344) rats, each group showing a different performance in the Morris maze test. After the application of an electrical tetanus (1 s, 100 Hz, 50 μA) in the stratum moleculare, a significant difference was found in the percent of induction of the dentate PTP in hippocampal slices obtained from rats of different strains and ages. In particular, the induction of the dentate PTP was significantly ( P < 0.01) higher in slices obtained from young SD or spontaneously SHR rats, having the better performance in the Morris maze than in slices obtained from old SD or F 344 rats or young WKY rats which had poorer performances in the Morris maze. On the contrary, no significant differences were found in the percent of induction of the LTP in the dentate area of hippocampal slices obtained from rats of different strains and ages. Moreover, after the application of an electrical tetanus (1 s, 100 Hz, 50 μA) in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages. The data show that the induction of hippocampal dentate high-frequency PTP is reduced not only in old rats but also in some peculiar strains of rats with impaired behavioral capability in the Morris maze.

Structure of the vitreoretinal border region in spontaneously hypertensive rats (SHR rats).

The morphology of the vitreoretinal border region, also termed the inner limiting membrane, was studied in spontaneously hypertensive rats (SHR rats), in Wistar Kyoto rats (WKY rats), and in Buffalo rats (BUF rats). The region was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in order to visualize a possible increase in thickness with raised arterial pressure. The median thickness of the lamina densa in TEM in the three groups varied from 34 to 68 nm. In hypertensive SHR rats the lamina densa showed thickening up to the 10th month and was unchanged thereafter. The same pattern was shown in WKY rats, although the thickness increased also after the tenth month in these controls. In BUF rats, however, the lamina densa decreased in thickness with age. The median thickness of the whole vitreoretinal border region varied between: SHR rats: 42 and 84 nm (SEM) and 51 and 127 nm (TEM); WKY rats: 84 nm (SEM) and 51 and 68 nm (TEM); BUF rats: 42 nm (SEM) and 34 and 68 nm (TEM). SHR rats showed in SEM an increase in thickness with age. In TEM, however, only one very old hypertensive rat had a thickened vitreoretinal border region. In WKY rats both SEM and TEM showed an increase in thickness with age, whereas BUF rats showed a decrease. Fundus photographs disclosed narrow, straight and irregular retinal arterioles in hypertensive SHR rats. Light microscopy of older SHR rats demonstrated retinal degeneration from the outer photoreceptor layer to the inner nuclear layer. This was also found in some of the older WKY rats.