Factors producing elevated core temperature in spontaneously hypertensive rats

Core temperature (Tco) of the spontaneously hypertensive rat (SHR) is consistently higher by approximately 1 degree C than that of normotensive controls. To analyze factors producing the elevated Tco, mean skin temperature (Tsk), metabolic heat production (M), respiratory evaporative heat loss (Eres), effective tissue thermal conductance (K), systolic blood pressure (BP), and Tco were determined in eight male SHR and nine male normotensive Wistar-Kyoto (WKY) rats habituated to rest quietly in neck stock restraint while exposed to ambient temperatures (Ta) of 12.5, 17, 23, 28.5, 32, 34, and 35 degrees C. At all temperatures steady-state BP, Tco, and M were higher for SHR's than for WKY's. SHR's could maintain thermal balance up to Ta 32 degrees C, and WKY's up to 34 degrees C. Eres from SHR's was greater than from WKY's at Ta of 12.5, 17, and 28.5 degrees C. K of SHR's was not different from or was higher than K of WKY's, and K for both groups was 2.6 times greater at Ta 32 degrees C than at 17 degrees C. These results indicate that the high Tco of SHR's is due to increased M uncompensated by increased K or Eres.     

剪切应力下内皮细胞内皮素及其mRNA的表达

应用Ｎｏｒｔｈｅｒｎ印迹方法研究高血压（ＳＨＲ）和正常（ＷＫＹ）大鼠脑微血管培养内皮细胞,在剪切应力０、０．５、１、２Ｐａ作用下２４ｈ后检测内皮素及其基因ｍＲＮＡ表达上的区别。结果表明,在剪切应力０、０．５、１Ｐａ下,ＷＫＹ大鼠的内皮细胞随着剪切应力加大,其内皮素水平及其基因的ｍＲＮＡ的表达均比ＷＫＹ相应组的为高。在剪切应力２Ｐａ时,ＷＫＹ和ＳＨＲ大鼠的内皮细胞内皮素及其基因的ｍＲＮＡ表达水平不同     

A comparison of the cutaneous microvascular properties of the Spontaneously Hypertensive rat and the Wistar-Kyoto rat

The Spontaneously Hypertensive rat (SHR) and its non-hypertensive companion strain, the Wistar-Kyoto (WKY) rat, provide an excellent comparative model to permit study of the differential properties of cutaneous microvascular beds. We explored the possibility that chronically elevated vascular pressures in the SHR rat might affect the microvascular constitution of the skin. We measured skin blood flow at the back and at the paw of a group of 20-week-old WKY rats and a contrast group of SHR rats. We then performed skin biopsies at these two locations and used the NIH Image program to count and measure the size of capillaries, arterioles, and venules. We also determined microvascular density as percentage of total tissue area. At basal temperature, skin blood flow was similar in the two rat strains at both the back and paw. Heat induced vasodilatation resulted in a 50% increase in blood flow at the back, reaching the same level in the two rat groups. However, at the paw site, thermal stimulation resulted in significantly greater flow (39.3 +/- 3.1 ml/100 gm tissue per min) in the SHR rats than the WKY rats (28.6 +/- 1.9 ml/100 gm tissue per min, P < 0.05). The ratio of systemic arterial pressure to skin blood flow was computed as an index of vascular resistance to flow. At basal temperature, this index was 50% greater for the SHR rats at both skin sites. At 44 degrees C, the resistance index decreased at both sites in both rat groups but was still approximately 50% higher at the back of the SHR than the WKY rats. In contrast, the resistance index at 44 degrees C at the paw site fell to the same level in both the SHR and WKY rats. There were twice as many capillaries at the back of the WKY rats than at the back of the SHR rats (9.2 +/- 2.0 per mm2 vs. 4.7 +/- 1.2 per mm2, P < 0.05). Expressed as a percentage of total tissue area, the capillary density at the back in the WKY rats was 0.064 +/- 0.010% as compared to 0.034 +/- 0.008% in the SHR rats (P < 0.05). There were five times more arterioles at the paw compared to the back in both rat groups with no significant difference between the groups. We measured the diameter of the lumen and the thickness of the wall of each arteriole and computed their ratio as an index of possible media hypertrophy. There were minimal differences seen in these parameters between the two rat groups at the back and paw sites. The venular density was significantly higher at the paw than at the back in both rat groups with no significant difference between them. Reduced capillary density at the back of the SHR rats may be a developmental adaptation to high blood pressure. Such a reduction in the pathways of blood flow may help account for increased flow resistance at that site, independent of arteriolar vasoconstriction.     

Myocardial hypertrophy of normotensive Wistar-Kyoto rats

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 +/- 0.03 mg/g, n = 41) was intermediate between SHR (2.82 +/- 0.04 mg/g, n = 47) and Wistar rats (1.98 +/- 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.     

Vascular flow capacity of hindlimb skeletal muscles in spontaneously hypertensive rats

Total and regional skeletal muscle flows (radiolabeled microspheres) were determined in isolated maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and age-matched (11-12 mo) normotensive Wistar-Kyoto rats (WKY) to assess the vascular flow capacity of the skeletal muscle vascular beds. Vascular flow capacity was estimated by measuring total hindquarters and regional muscle blood flows (under conditions of maximal vasodilation with papaverine or papaverine plus isoproterenol) over a wide range of perfusion pressures in WKY and SHR. Capillary exchange capacity was estimated by determining the capillary filtration coefficient. Isogravimetric capillary pressures and segmental vascular resistances were determined in each hindquarter. Isogravimetric flows and capillary pressures were not different between WKY and SHR. However, total and precapillary vascular resistances were significantly elevated in SHR, and postcapillary resistances were not different compared with WKY. Maximal capillary filtration coefficient values for the SHR group averaged 20% lower than WKY values, suggesting that hypertension was associated with a reduction in the microvascular surface area available for fluid exchange and, therefore, the capillary exchange capacity. Over the perfusion pressures studied, total hindquarters flows averaged 60% lower in SHR than in WKY. Flows to individual skeletal muscles averaged 76% lower in SHR than in WKY regardless of the muscle fiber type. Thus, modifications exist in the hindlimb skeletal muscle vasculature of SHR that reduces the capillary exchange capacity and limit the capacity of deliver flow at a given perfusion pressure gradient.     

Spontaneously hypertensive and Wistar Kyoto rats are genetically disparate.

Spontaneously hypertensive rats (SHR) are one of the most common animal models used to study essential hypertension in humans. Because SHR and normotensive Wistar Kyoto (WKY) rats were both established from the same parental, normotensive Wistar stock, WKY animals have been used almost exclusively as control animals in studies of SHR. Recently, the suitability of WKY rats as normotensive controls for SHR has been challenged. To establish whether or not SHR and WKY rats share the same immunologic backgrounds, we initially performed a series of skin grafting experiments on these animals. In all cases, grafts of SHR donor skin to WKY recipients and of WKY donor skin to SHR recipients resulted in complete rejection within 7 to 10 days. In addition, grafts of WKY donor skin to other WKY recipients resulted in graft rejection. By contrast, skin grafts between SHRs were always accepted. To further characterize the genetic distinctions between SHR and WKY rats, allelic profiles based on a series of immunologic and biochemical markers were established for each strain. These findings clearly establish that SHR and WKY rats differ at the major histocompatibility complex, in specific blood group antigens, and in a panel of isozymic markers. Moreover, whereas SHRs have the same genetic profiles irrespective of source, some colonies of WKY rats are outbred, as judged by their variant allelic profiles.     

Characteristics of central binding sites for [3H] DAMGO in spontaneously hypertensive rats

The binding of [3H] DAMGO, a highly selective ligand for mu-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. [3H] DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (Bmax value) and apparent dissociation constant (Kd value) of [3H] DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The Bmax value of [3H] DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the Kd values in the two strains did not differ. On the other hand, the Bmax value of [3H] DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the Kd values in the two strains were similar. It is concluded that SHR rats have higher density of mu-opiate receptors in hypothalamus and midbrain but lower density in amygdala in comparison with WKY rats, and that such differences in the distribution of mu-opiate receptors may be related to the elevated blood pressure in SHR rats.     

自发性高血压大鼠中枢去甲肾上腺素与血管紧张...

The norepinephrine (NE) and angiotensin II (A II) contents in the brain regions of SHR and WKY (Wistar Kyoto) rats at different ages were determined by fluorospectrophotometry and radioimmunoassay. The systolic blood pressure (SBP) of the rats was measured indirectly with a tail cuff technique in conscious state. The results were as follows: There was no significant difference in the central A II and NE contents between SHR and WKY rats at 8-week age. Since 12th week age the SBP of SHR has increased gradually, up to 16th to 20th week and then maintained steady level. Whereas there was no significant change of SBP in WKY rats in the same span of age. In the early and late states of hypertension the A II contents in the medulla oblongata, pons, hypothalamus and nucleus caudatus of SHR were markedly higher than those of the age-matched WKY rats. But the change of NE content of SHR in the early stage showed a different picture as compared with that of WKY rats, i.e., NE decreased in medulla oblongata and anterior hypothalamus but increased in pons, posterior hypothalamus and nucleus caudatus. However, in the late stage there was no such significant difference between SHR and WKY rats. Consequently, it is suggested that the central A II and NE participated in the development of hypertension of SHR, and that the maintenance of hypertension is mainly dependent upon the increased A II content. Microinjection of captopril or 6-OHDA in the lateral cerebroventricle of SHR elicited a decrease of BP and reduction of both A II and NE contents in the medulla and hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient middle cerebral artery occlusion causes different structural, mechanical, and myogenic alterations in normotensive and hypertensive rats

Transient focal cerebral ischemia in the rat alters vessel properties, and spontaneously hypertensive rats (SHR) show a poorer outcome after ischemia. In the present study we examined the role of hypertension on vessel properties after ischemia-reperfusion. The right middle cerebral artery (MCA) was occluded (90 min) and reperfused (24 h) in SHR (n = 12) and Wistar-Kyoto rats (WKY; n = 11). Sham-operated rats (SHR, n = 10; WKY, n = 10) were used as controls. The structural, mechanical, and myogenic properties of the MCA were assessed by pressure myography. Nuclei distribution and elastin content and organization were analyzed by confocal microscopy. Infarct volume was larger in SHR than in WKY rats. Ischemia-reperfusion induced adventitial hypertrophy associated with an increase in the total number of adventitial cells. In addition, fenestrae area and arterial distensibility increased and myogenic tone decreased in the MCA of WKY rats after ischemia-reperfusion. Hypertension per se induced hypertrophic inward remodeling. Ischemia-reperfusion decreased the cross-sectional area of the MCA in SHR, without significant changes in distensibility, despite an increase in fenestrae area. In addition, MCA myogenic properties were not altered after ischemia-reperfusion in SHR. Our results indicate that in normotensive rats, MCA develops a compensatory mechanism (i.e., enhanced distensibility and decreased myogenic tone) that counteracts the effect of ischemia-reperfusion and ensures correct cerebral irrigation. These compensatory mechanisms are lost in hypertension, thereby explaining, at least in part, the greater infarct volume observed in SHR.     

Sodium homeostasis in transplanted rats with a spontaneously hypertensive rat kidney

Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To investigate whether renal sodium retention precedes the development of posttransplantation hypertension in recipients of an SHR kidney on a standard sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR x WKY F1 hybrids, measured daily sodium balances during the first 12 days after removal of both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk. Recipients of an SHR kidney (n = 12) retained more sodium than recipients of a WKY kidney (n = 12) (7.3 +/- 10 vs. 4.0 +/- 0.7 mmol, P < 0.05). MAP was 144 +/- 6 mmHg in recipients of an SHR kidney and 106 +/- 5 mmHg in recipients of a WKY kidney (P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of recipients of an SHR kidney (n = 10) did not prevent posttransplantation hypertension (MAP, 142 +/- 4 mmHg). Urinary endothelin and urodilatin excretion rates were similar in recipients of an SHR and a WKY kidney. Transient excess sodium retention after renal transplantation may contribute to posttransplantation hypertension in recipients of an SHR kidney.     

Decrease in urinary excretion of active kallikrein in conscious young and adult spontaneously hypertensive rats

Urinary excretion of active kallikrein was determined every day (amidolytic assay) in 6 male Okamoto-Aoki spontaneously hypertensive rats (SHR) and 6 male normotensive Wistar-Kyoto rats (WKY) from ages 4 to 7 weeks and from 12 to 15 weeks. The rats were housed in individual metabolic cages and were allowed free access to food having normal sodium content and to tap water. Urinary kallikrein excretion was lower in 4-week-old SHR than in age-matched WKY (7.8 +/- 1.4 vs. 15.5 +/- 2.3 nkat/24 h respectively, P less than 0.01) at a moment when systolic blood pressure (BP) in SHR was already higher than in WKY. The slope of the increase in active kallikrein excretion from week 4 to 7 was not different for SHR and WKY (6.34 +/- 1.05 vs. 7.50 +/- 1.02 nkat/24 h-1 . wk-1 respectively). In contrast, from week 12 to 15, this slope was not significant for SHR (1.67 +/- 2.55 nkat/24 h-1 . wk-1) while it remained positive in WKY (7.36 +/- 3,44 nkat/24 h-1 . wk-1). In both SHR and WKY, urinary kallikrein excretion was directly related to BP from week 4 to 7 but the slope of the regression line was less for SHR than for WKY (0.19 +/- 0.05 vs. 0.48 +/- 0.12 nkat/24 h-1 . mm Hg respectively). From ages 12 to 15 weeks, kallikrein excretion was still related to pressure in WKY (y = 1.92 x - 180.8; r = 0.93) but not in SHR (y = 0.71 x - 81.48; r = 0.52).(ABSTRACT TRUNCATED AT 250 WORDS)     

正常大鼠植入高血压大鼠肾脏后 动脉血压的变化

本实验对12周龄的自发性高血压大鼠(spontaneously hypertensive rat,SHR)及其对照组Wistar Kyoto (WKY)大鼠进行了肾脏移植的研究, 并观察受肾移植大鼠动脉血压的变化以及免疫抑制剂对动脉血压的影响。 用尾套法对接受同窝另一同胞WKY大鼠肾脏移植且存活5周的6只WKY大鼠(A组)及接受SHR肾脏移植且存活5周的6只WKY大鼠(B组)的尾动脉收缩压进行检测, 移植前A、 B两组受肾移植大鼠的尾动脉收缩压分别为18.0±0.93 和18.3±0.68 kPa,无统计学显著差异(P>0.05); 移植后3、 4、 5周时, B组大鼠的尾动脉收缩压显著高于A组大鼠, 移植后5周时, A, B两组大鼠的收缩压分别为19.0±0.71 和23.0±0.69 kPa (P<0.001); 所用剂量的免疫抑制剂CsA对双侧肾脏完整以及右侧肾脏切除的SHR、 WKY大鼠的动脉血压无显著影响。 以上结果表明, SHR的肾脏在高血压的形成中可能起重要作用。     

Effects of angiotensin II type 1 receptor blockade on the oxidative stress in spontaneously hypertensive rat tissues

The aim of this work was to investigate the production of oxidative damage in homogenized kidney, liver and brain of spontaneously hypertensive rats (SHR), as well as the involvement of angiotensin (Ang) II in this process. Groups of 12-week-old SHR and Wistar Kyoto rats (WKY) were given 10 mg/kg/day losartan in the drinking water during 14 days. Other groups of WKY and SHR without treatment were used as controls. The production of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were determined. No significant difference in TBARS was observed between untreated SHR or WKY rats; GSH content was lower in the liver but higher in the brain of SHR compared to WKY rats. In tissues from the SHR group, SOD and Gpx activities were reduced, whereas CAT activity was slightly increased in kidney. TBARS levels did not change in WKY rats after losartan administration, but were reduced in SHR liver and brain. Losartan treatment decreased GSH content in WKY kidney, but increased GSH in SHR liver. The activity of the antioxidant enzymes was not modified by losartan in WKY rats; however, their activities increased in tissues from treated SHR. The lower activity of antioxidant enzymes in tissues from hypertensive rats compared to those detected in normotensive controls, indicates oxidative stress production. Ang II seems to play no role in this process in normotensive animals, although AT1 receptor blockade in SHR enhances the enzymatic activity indicating that Ang II is implicated in oxidative stress generation in the hypertensive animals.     

正常大鼠植入高血压大鼠肾脏后动脉血压的变化

本实验对12周龄的自发性高血压大鼠(spontaneouslyhypertensiverat,SHR)及其对照组WistarKyoto(WKY)大鼠进行了肾脏移植的研究,并观察受肾移植大鼠动脉血压的变化以及免疫抑制剂对动脉血压的影响。用尾套法对接受同窝另一同胞WKY大鼠肾脏移植且存活5周的6只WKY大鼠(A组)及接受SHR肾脏移植且存活5周的6只WKY大鼠(B组)的尾动脉收缩压进行检测,移植前A、B两组受肾移植大鼠的尾动脉收缩压分别为180±093和183±068kPa,无统计学显著差异(P>005);移植后3、4、5周时,B组大鼠的尾动脉收缩压显著高于A组大鼠,移植后5周时,A,B两组大鼠的收缩压分别为190±071和230±069kPa(P<0001);所用剂量的免疫抑制剂CsA对双侧肾脏完整以及右侧肾脏切除的SHR、WKY大鼠的动脉血压无显著影响。以上结果表明,SHR的肾脏在高血压的形成中可能起重要作用     

Proliferation of thyrotropin releasing hormone receptors in specific brain regions during the development of hypertension in spontaneously hypertensive rats

The binding of [3H] [3-MeHis2] thyrotropin releasing hormone [( 3H]MeTRH) to brain membranes prepared from 8 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. [3H]MeTRH bound specifically to rat brain membranes at a single high affinity site. The density (Bmax value) of [3H]MeTRH binding sites was significantly greater (28%) in SHR rats compared to WKY rats. The apparent dissociation constants (Kd values) for the binding of [3H]MeTRH in SHR and WKY rats did not differ. Binding in the various brain regions revealed that the density of [3H]MeTRH was highest in the hypothalamus followed in decreasing order by pons + medulla, midbrain, cortex and striatum. The binding of [3H]MeTRH was approximately 25% greater in cortex, hypothalamus and striatum of SHR rats in comparison to WKY rats. The binding in pons + medulla, midbrain and pituitary of SHR and WKY rats did not differ. To assess the significance of increased binding sites for [3H]MeTRH in some brain regions of SHR rats, the binding studies were carried out during normotensive and hypertensive stages of postnatal age in the two strains. In 3 and 4 week old SHR rats there was neither an increase in blood pressure nor any increase in [3H]MeTRH binding in the hypothalamus and striatum as compared to age matched WKY rats. With the development of elevated blood pressure at 6 weeks, an increase in [3H]MeTRH binding in the hypothalamus and striatum of SHR rats in comparison to the tissues from WKY rats was observed. The results provide, for the first time, evidence for a parallel increase in the density of brain TRH receptors with elevation of blood pressure, and suggest that brain TRH receptors may play an important role in the pathophysiology of hypertension.     

Cold-restraint induced gastric lesions in normotensive and spontaneously hypertensive rats

Spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats were subjected to 2 hr of cold-restraint stress at 2–6°C following a 24 hr fast. WKY rats had a significantly greater incidence and degree of ulceration of the gastric glandular mucosa than did SHR rats. Mean arterial pressure, obtained from a chronic arterial cannula, fell during 2 hr of cold-restraint stress in both SHR and WKY rats. Heart rate was unchanged in WKY but fell significantly in SHR. Plasma norepinephrine (NE) and epinephrine (E), determined by radioenzymatic assay, increased significantly following stress. Increased levels of NE remained similar for both SHR and WKY rats, while post-stress levels of E for the SHR rats greatly exceeded E levels for WKY rats. A greater degree of hypothermia was also noted in SHR rats. Decreased stress induced ulcerogenesis in the SHR may be due to the well-known altered hemodynamic and autonomic nervous system reactivity in this strain or other factors not yet discovered.     

Dynamic characteristics of baroreflex neural and peripheral arcs are preserved in spontaneously hypertensive rats

Although baroreceptors are known to reset to operate in a higher pressure range in spontaneously hypertensive rats (SHR), the total profile of dynamic arterial pressure (AP) regulation remains to be clarified. We estimated open-loop transfer functions of the carotid sinus baroreflex in SHR and Wistar Kyoto (WKY) rats. Mean input pressures were set at 120 (WKY??? and SHR???) and 160 mmHg (SHR???). The neural arc transfer function from carotid sinus pressure to efferent splanchnic sympathetic nerve activity (SNA) revealed derivative characteristics in both WKY and SHR. The slope of dynamic gain (in decibels per decade) between 0.1 and 1 Hz was not different between WKY??? (10.1 ± 1.0) and SHR??? (10.4 ± 1.1) but was significantly greater in SHR??? (13.2 ± 0.8, P < 0.05 with Bonferroni correction) than in SHR???. The peripheral arc transfer function from SNA to AP showed low-pass characteristics. The slope of dynamic gain (in decibels per decade) did not differ between WKY??? (-34.0 ± 1.2) and SHR??? (-31.4 ± 1.0) or between SHR??? and SHR??? (-32.8 ± 1.3). The total baroreflex showed low-pass characteristics and the dynamic gain at 0.01 Hz did not differ between WKY??? (0.91 ± 0.08) and SHR??? (0.84 ± 0.13) or between SHR??? and SHR??? (0.83 ± 0.11). In both WKY and SHR, the declining slope of dynamic gain was significantly gentler for the total baroreflex than for the peripheral arc, suggesting improved dynamic AP response in the total baroreflex. In conclusion, the dynamic characteristics of AP regulation by the carotid sinus baroreflex were well preserved in SHR despite significantly higher mean AP.     

Excess Salt Increases Infarct Size Produced by Photothrombotic Distal Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats

Cerebral circulation is known to be vulnerable to high salt loading. However, no study has investigated the effects of excess salt on focal ischemic brain injury. After 14 days of salt loading (0.9% saline) or water, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to photothrombotic middle cerebral artery occlusion (MCAO), and infarct volume was determined at 48 h after MCAO: albumin and hemoglobin contents in discrete brain regions were also determined in SHR. Salt loading did not affect blood pressure levels in SHR and WKY. After MCAO, regional cerebral blood flow (CBF), determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning), was more steeply decreased in the salt-loaded group than in the control group. In SHR/Izm, infarct volume in the salt-loaded group was 112±27 mm³, which was significantly larger than 77±12 mm³ in the control group (p = 0.002), while the extents of blood-brain barrier disruption (brain albumin and hemoglobin levels) were not affected by excess salt. In WKY, salt loading did not significantly increase infarct size. These results show the detrimental effects of salt loading on intra-ischemic CBF and subsequent brain infarction produced by phototrhombotic MCAO in hypertensive rats.     

Incidence of multinucleated and polyploid aortic smooth muscle cells cultured from different age groups of spontaneously hypertensive rats.

Cell size and incidence of multinucleated, polyploid cells in cultured aortic smooth muscle cells from different age groups of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were compared. Smooth muscle cells from SHR were generally larger than those from WKY, and the percentage of multinucleated smooth muscle cells was always higher in SHR than WKY in the three age groups of rats studied (3-4, 10-12, and 28-30 weeks). In smooth muscle cells from the 3- to 4-week group, there was a positive correlation between cell diameter and the percentage of multinucleated smooth muscle cells. Microdensitometric measurements also showed that the incidence of polyploid smooth muscle cells was always higher in SHR than WKY in the three age groups. There was a positive correlation between DNA density and nuclear area measurements in all the age groups of SHR and WKY. We conclude that cultured aortic smooth muscle cells from different age groups of SHR and WKY contained heterogeneous populations of cells and that, under our culture conditions, the polyploidy of the smooth muscle cells found in vivo was maintained in the SHR and WKY.     

Spontaneously hypertensive rats exhibit supersensitivity to the hypertensive and hyperthermic effects of thyrotropin releasing hormone

The effect of thyrotropin releasing hormone (TRH) on colonic temperature and systolic blood pressure of age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. Administration of TRH produced dose-dependent increases in body temperature and systolic blood pressure. TRH-induced changes in both responses were of greater magnitude in SHR rats compared to WKY rats. The results provide the first evidence that SHR rats exhibit supersensitivity to non-neuroendocrinological effects of TRH and that TRH may play a role in the pathophysiology of elevated blood pressure.