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.     

Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

The binding of 3H-naltrexone, an opiate receptor antagonist, 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-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of 3H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (Bmax value) and apparent dissociation constant (Kd value) values of 3H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midbrain, cortex and spinal cord of WKY and SHR rats did not differ. The Bmax value of 3H-naltrexone binding to membranes of hypothalamus of SHR rats was 518% higher than WKY rats but the Kd values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with 3H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.     

Kinin B1 and B2 receptor mRNA expression in the hypothalamus of spontaneously hypertensive rats

The central hypertensive effects induced by bradykinin are known to be mediated via B2 receptors, which are present constitutively in the brain. B, receptors are rapidly upregulated during inflammation, hyperalgesia, and experimental diabetes. The hypothalamus plays an important role in the regulation of cardiovascular homeostasis, and all components of kallikrein-kinin system have been identified in this area. Therefore, we analyzed the mRNA expression of B1 and B2 receptors in the hypothalamus of spontaneously hypertensive rats (SHR) by RT-PCR. Male SHR were studied at three different ages corresponding to the three phases in the development of hypertension: (i) 3-4 (prehypertensive), (ii) 7-8 (onset of hypertension), and (iii) 12-13 weeks (established hypertension) after birth, and compared with age-matched Wistar-Kyoto (WKY) rats. At all ages tested, B2 receptor mRNA levels in the hypothalamus of SHR were higher than age-matched WKY rats (p < 0.001). However, the B1 receptor mRNA levels were higher at the established phase of hypertension only. We conclude that B1 and B2 receptor mRNA are differentially expressed in the hypothalamus of SHR and may play different roles in the pathogenesis of hypertension: upregulation of B2 receptor mRNA from early age may participate in the pathogenesis of hypertension, whereas an upregulation of B1 receptor mRNA in the established phase of hypertension may reflect an epiphenomenon in essential hypertension.     

Reduction of ventricular hypertrophy and fibrosis in spontaneously hypertensive rats by L-arginine

The purpose of this experiment was to explore long-term L-arginine administration on ventricular hypertrophy and cardiac fibrosis in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Twenty-four rats of each strain at eight wks of age were divided into two groups--one receiving L-arginine and the other vehicle for twelve wks. Arterial pressure (AP) and heart rate were monitored. At 20 wks of age, the rats' rings of thoracic aorta were isolated to record isometric tension. The study measured left ventricular weight (LVW), body weight (BW), left ventricular (LV) contents of cGMP, and collagen volume fraction (LVCVF). Histological examination of the LV tissue determined changes in cardiomyocytes. Administration of L-arginine did not alter the AP change in SHR, but reduced the AP in WKY after six wks. Our results showed a significantly higher LVW/BW ratio and LVCVF in vehicle-treated SHR compared to levels in corresponding WKY, whereas, the LV cGMP and nitrite/nitrate measurements were higher in vehicle-treated WKY than in SHR. L-Arginine treatment decreased LVW/BW ratio and LVCVF, while increasing the levels of LV cGMP and nitrite/nitrate only in SHR, consistent with histopathological examinations that showed L-arginine prevented cardiomyocytes from thickness and hypertrophy. Our results suggested that the mechanism of reduction in ventricular hypertrophy and fibrosis following long-term L-arginine administration in SHR may stem from increased myocardial nitric oxide-cGMP signaling, independent of AP and EDV of thoracic aorta.     

Vasopressin receptors and inositol trisphosphate production in blood vessels of spontaneously hypertensive rats

To understand the regulation of vasopressin (AVP) receptors in spontaneous hypertension, we investigated the pressor response of AVP in the perfused mesenteric vasculature, AVP binding sites in the membrane preparation of the same vascular bed, and the production of inositol trisphosphate (InsP3) stimulated by AVP in the aorta of spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and Wistar rats (WR) at different ages (4-16 weeks). Plasma AVP concentrations were similar in SHR, WKY, and WR at all ages. The density of AVP vascular binding sites was significantly higher in WKY than in SHR and WR at 12 weeks. Receptor affinity was similar in all strains. The pressor response of the mesenteric vasculature to AVP was similar in the three strains of rats at 4 weeks (prehypertensive stage) and increased progressively in SHR compared with WKY and WR at 8 and 12 weeks of age by 43 and 35%, respectively, and by more than 80% at 16 weeks of age (established hypertensive stage). There was no difference in vascular sensitivity to AVP. A significantly increased pressor response to a supramaximal dose of norepinephrine was also found at 16 weeks in SHR, but not in younger rats. InsP3 production in the aorta in response to AVP was increased in SHR at 8, 12, and 16 weeks, compared with WKY and WR. These results suggest that the vascular response to AVP is increased in SHR, in spite of decreased or normal density of binding sites compared with WKY or WR.(ABSTRACT TRUNCATED AT 250 WORDS)     

L-carnitine attenuates oxidative stress in hypertensive rats

The present study aimed to investigate whether l-carnitine (LC) protects the vascular endothelium and tissues against oxidative damage in hypertension. Antioxidant enzyme activities, glutathione and lipid peroxidation were measured in the liver and heart of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Nitrite and nitrate levels and total antioxidant status (TAS) were evaluated in plasma, and the expression of endothelial nitric oxide synthase (eNOS) and p22phox subunit of NAD(P)H oxidase was determined in aorta. Glutathione peroxidase activity was lower in SHR than in WKY rats, and LC increased this activity in SHR up to values close to those observed in normotensive animals. Glutathione reductase and catalase activities, which were higher in SHR, tended to increase after LC treatment. No differences were found in the activity of superoxide dismutase among any animal group. The ratio between reduced and oxidized glutathione and the levels of lipid peroxidation were respectively decreased and increased in hypertensive rats, and both parameters were normalized after the treatment. Similarly, LC was able to reverse the reduced plasma nitrite and nitrate levels and TAS observed in SHR. We found no alterations in the expression of aortic eNOS among any group; however, p22phox mRNA levels showed an increase in SHR that was reversed by LC. In conclusion, chronic administration of LC leads to an increase in hepatic and cardiac antioxidant defense and a reduction in the systemic oxidative process in SHR. Therefore, LC might increase NO availability in SHR aorta by a reduction in superoxide anion production.     

Brain opiate receptor concentrations are increased in adult spontaneously hypertensive rats.

The saturable binding of 3H-naltrexone in the brains of eight week old spontaneously hypertensive rats (SHR) is about twice that measured in corresponding normotensive WKY rats. This increase is dependent on age since in three and four week old SHR and WKY rats no difference in binding is observed. Scatchard analysis of the saturation curves for the adult animals revealed that the change in binding is due to an increase in the number of binding sites and does not reflect a difference in binding affinity. The increase in opiate receptor content of SHR rats coincides with the appearance of elevated blood pressure in these animals, and supports a concept in which an interaction between the endorphins and the endocrine system may be involved in the mechanisms controlling hypertension.     

Muscarinic cholinoceptors and choline acetyltransferase activity in the hypothalamus of spontaneously hypertensive rats

To study the role of central cholinergic mechanisms in hypertension, we have determined muscarinic receptors using [³H](-)quinuclidinyl benzilate (QNB) and choline acetyltransferase (ChAT) activity in the brain regions of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and renal hypertensive rats. The number of muscarinic receptors was significantly (33–38%) elevated in the hypothalamus of SHR and SHRSP at the ages of 16 and 24 weeks compared to that of Wistar-Kyoto rats (WKY). An increased density of muscarinic receptors was consistently observed in the prehypertensive (5 weeks) and developmental (10 weeks) stages of hypertension. In contrast, in the hypothalamus of rats with renal hypertension there was no muscarinic receptor alteration. The receptor alteration in the SHRSP hypothalamus was not abolished by a chronic hypotensive treatment which prevented the development of hypertension, suggesting that an enhancement of the muscarinic receptors in spontaneous hypertension does not occur secondarily to the elevation of blood pressure. The hypothalamus of SHR and SHRSP at the ages of 5 and 24 weeks showed significantly less activity of ChAT. These data demonstrate that there is a specific increase in muscarinic receptors and a decrease in cholinergic activity in the hypothalamus of SHR and SHRSP. Thus, the present study suggests an important role for hypothalamic cholinergic receptors in the pathogenesis of spontaneous hypertension.     

Renal Na+-K+-ATPase in weanling and adult spontaneously hypertensive rats

The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K+-ATPase activity (mumole PO4/mg protein/hr) were studied in 9 weanling normotensive spontaneously hypertensive rats (SHR), 9 adult hypertensive SHR, and 9 weanling and 9 adult normotensive Wistar-Kyoto rats (WKY). All groups were placed on a normal (0.4% sodium) diet. PRA and plasma aldosterone, measured in samples drawn from the ether-anesthetized rat, were higher in weanling SHR (15.2 +/- 2.0, 37 +/- 4.2) than in WKY. PRA measured in samples collected from a separate group of unanesthetized weanling SHR was also greater than in age-matched WKY. In adult SHR, PRA (6.1 +/- 0.9) and plasma aldosterone (20.0 +/- 2.7) were decreased. During the weanling period Na+-K+-ATPase activity in SHR was not only greater than in age-matched WKY but was also increased compared to adult normotensive and hypertensive rats (137 +/- 9 weanling SHR, 89 +/- 7 weanling WKY, 73 +/- 11 adult SHR, 84 +/- 17 adult WKY). Thus, during the weanling period the renin-angiotensin-aldosterone (R-A-A) system and renal Na+-K+-ATPase activity are activated in SHR. The elevation of Na+-K+-ATPase activity may be due to increased aldosterone levels. It was noted, however, that plasma aldosterone was similar in adult WKY and weanling SHR, while Na+-K+-ATPase activity was higher in SHR. These findings involving R-A-A and renal Na+-K+-ATPase activity prior to the elevation of blood pressure suggest that the kidneys may play a role in the initiation of hypertension in SHR.     

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.     

Chronic effects of angiotensin-converting enzyme inhibition on kinin receptor binding sites in the rat spinal cord

With the use of in vitro receptor autoradiography, this study aims at determining whether the higher level of kinin B(2) receptor density in the spinal cord of the spontaneously hypertensive rat (SHR) is secondary to arterial hypertension and whether chronic treatment with angiotensin I-converting enzyme inhibitors (ACEI) can regulate neuronal B(1) and B(2) receptors. SHR received, from the age of 4 wk, one of the two ACEI (lisinopril or zofenopril, 10 mg x kg(-1) x day(-1)) or for comparison, the selective AT(1) antagonist (losartan, 20 mg x kg(-1) x day(-1)) in their drinking water for a period of 4, 12, and 20 wk. Age-matched untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. B(2) receptor binding sites in most laminae were higher in SHR than in WKY from the age of 8 to 24 wk. Whereas B(1) receptor binding sites were significantly present in young SHR and WKY, they were barely detectable in adult rats. ACEI (16 and 24 wk) and AT(1) antagonist (24 wk) enhanced the number of B(2) without changing B(1) receptor binding sites. However, at 8 wk the three treatments significantly increased B(1) and decreased B(2) receptors in lamina I. It is concluded that 1) the higher density of B(2) receptors in the spinal cord of SHR is not due to hypertension, 2) kinin receptors are regulated differently by ACEI in neuronal and vascular tissues, and 3) aging may have a profound impact on levels of B(1) and B(2) receptors in the rat spinal cord.     

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.     

Plasticity of pre- and postsynaptic GABAB receptor function in the paraventricular nucleus in spontaneously hypertensive rats

GABA(B) receptor function is upregulated in the paraventricular nucleus (PVN) of the hypothalamus in spontaneously hypertensive rats (SHR), but it is unclear whether this upregulation occurs pre- or postsynaptically. We therefore determined pre- and postsynaptic GABA(B) receptor function in retrogradely labeled spinally projecting PVN neurons using whole cell patch-clamp recording in brain slices in SHR and Wistar-Kyoto (WKY) rats. Bath application of the GABA(B) receptor agonist baclofen significantly decreased the spontaneous firing activity of labeled PVN neurons in both SHR and WKY rats. However, the magnitude of reduction in the firing rate was significantly greater in SHR than in WKY rats. Furthermore, baclofen produced larger membrane hyperpolarization and outward currents in labeled PVN neurons in SHR than in WKY rats. The baclofen-induced current was abolished by either including G protein inhibitor GDPbetaS in the pipette solution or bath application of the GABA(B) receptor antagonist in both SHR and WKY rats. Blocking N-methyl-d-aspartic acid receptors had no significant effect on baclofen-elicited outward currents in SHR. In addition, baclofen caused significantly greater inhibition of glutamatergic excitatory postsynaptic currents (EPSCs) in labeled PVN neurons in brain slices from SHR than WKY rats. By contrast, baclofen produced significantly less inhibition of GABAergic inhibitory postsynaptic currents (IPSCs) in labeled PVN neurons in SHR than in WKY rats. Although microinjection of the GABA(B) antagonist into the PVN increases sympathetic vasomotor tone in SHR, the GABA(B) antagonist did not affect EPSCs and IPSCs of the PVN neurons in vitro. These findings suggest that postsynaptic GABA(B) receptor function is upregulated in PVN presympathetic neurons in SHR. Whereas presynaptic GABA(B) receptor control of glutamatergic synaptic inputs is enhanced, presynaptic GABA(B) receptor control of GABAergic inputs in the PVN is attenuated in SHR. Changes in both pre- and postsynaptic GABA(B) receptors in the PVN may contribute to the control of sympathetic outflow in hypertension.     

Influence of active immunization against angiotensin AT1 or AT2 receptor on hypertension development in young and adult SHR

The influence of long-lasting blockade of angiotensin AT1 or AT2 receptors by antibody against the particular receptor peptides on blood pressure and relative heart and kidney weight was studied in spontaneously hypertensive rats (SHR). Young and adult SHR were repeatedly immunized against the sequence 14-23 of angiotensin AT1 receptor from the age of either 1 or 3 months. Other groups of young and adult SHR were immunized against the sequences 37-43 and 106-116 of angiotensin AT2 receptor. Synthetic peptides conjugated to bovine gamma globulin were used as antigens. After 5 months of immunization, blood pressure was measured by the direct method. All immunized animals produced antibodies against the particular peptides. At the end of immunization, the blood pressure was significantly decreased in SHR immunized in youth against angiotensin AT1 receptor peptide, although no difference in heart and kidney hypertrophy was observed compared to sham-immunized SHR. The immunization against angiotensin AT1 receptor peptide in adulthood as well as the immunization against angiotensin AT2 receptor peptides in youth or in adulthood affected neither blood pressure nor heart and kidney weight. No influence of immunization on the studied parameters was observed in normotensive WKY rats. Angiotensin AT1 receptors play a more important role in the pathogenesis of spontaneous hypertension than angiotensin AT2 receptors. The blockade of angiotensin AT1 receptors by active immunization against the receptor peptide attenuated hypertension development in young SHR but did not modify the already established hypertension in adult SHR.     

Atrial natriuretic peptide and angiotensin II binding sites in cerebral capillaries of spontaneously hypertensive rats

1. We carried out investigations on specific atrial natriuretic peptide (ANP) and angiotensin II (ANG) binding sites in capillaries isolated from the cerebral cortex of spontaneously hypertensive rats (SHR), an animal model of human essential hypertension, and also from Wistar Kyoto rats (WKY). 2. In an equilibrium binding study done in the presence of increasing concentrations of the radiolabeled ligands, the binding of 125I-rat alpha-ANP (1-28) [ANF-(99-126)] (125I-rANP) and 125I-ANG (5-L-isoleucine) (125I-ANG) to the cerebral capillaries was single and of a high affinity. 3. The maximum binding capacity (Bmax) and dissociation constant (Kd) in the 125I-rANP binding of 20-week-old, hypertensive SHR was significantly lower than in age-matched, normotensive WKY. Conversely, a significant increase in the Bmax of 125I-ANG binding of adult SHR was observed, with a significant decrease in the Kd. 4. There was no differences in the Bmax of 125I-rANP and 125I-ANG binding between 4-week-old, prehypertensive SHR and age-matched WKY. However, there was a significant decrease in the Kd of 125I-rANP binding of SHR. 5. As a dramatic change in the binding kinetics of 125I-rANP and 125I-ANG was noted in the cerebral capillaries of adult sustained-hypertensive SHR, the possibility that ANP and ANG play a role in the etiology of dysfunction of the blood-brain barrier complicated with hypertension, by interacting with specific receptors, would have to be considered.     

On the role of NMDA receptors in blood pressure regulation in spontaneously hypertensive rats (SHR)

Summary In the present study the binding of [³H]MK-801 to glutamatergic receptors of the NMDA type was compared in spontaneously hypertensive (SHR) and normotensive (WKY) rats in various brain structures (including nucleus tractus solitarii) by quantitative receptor autoradiography. Additionally, blood pressure changes after treatment with the NMDA antagonist MK-801 were studied in both strains. There were no differences between SHR and WKY rats either in the level of [³H]MK-801 binding or in the hypertensive reaction to MK-801.     

Norepinephrine concentration in kidneys of normotensive Wistar-Kyoto and spontaneously hypertensive rats.

Renal norepinephrine (NE) concentration was measured in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) at 7, 9, 11, and 13 weeks of age. Although the weight of kidneys was similar in the two strains of rats, renal NE concentration was significantly lower in SHR at all ages (147 +/- 9 to 175 +/- 13 ng/g for SHR, and 216 +/- 8 to 262 +/- 17 ng/g for WKY rats). The difference in renal NE concentration during this time of rapidly increasing arterial pressure in the SHR suggests that renal NE may in some way be related to the development of hypertension.     

Atrial natriuretic polypeptide (ANP) in the development of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP)

In order to investigate the pathophysiological role of atrial natriuretic polypeptide (ANP) in genetic hypertensive rats, the atrial content and plasma concentration of ANP were measured by a sensitive radioimmunoassay (RIA) for rat ANP in 5-, 10- and 20-week-old spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared to age-matched Wistar Kyoto rats (WKY). Atrial content of immunoreactive ANP (ir-ANP) tended to be higher in SHR and was already significantly higher in SHRSP than in WKY at 5 weeks of age. Atrial content in the hypertensive strains became significantly higher than in WKY when hypertension developed at 10 and 20 weeks. On the other hand, plasma ir-ANP in SHR was significantly lower than in WKY at 5 weeks, however, it became significantly higher in both SHR and SHRSP than in WKY at 10 and 20 weeks. These findings suggest that ANP release may increase to compensate for the elevation of blood pressure in SHR and SHRSP and that biosynthesis of ANP may be concomitantly stimulated, resulting in an increase in atrial ANP.     

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     

Plasma concentrations of endothelin-1 in spontaneously hypertensive rats and DOCA-salt hypertensive rats

To investigate the possible involvement of endothelin-1 (ET-1), an endothelium-derived potent vasoconstrictor peptide, in the pathophysiology of hypertension, plasma ET-1 levels in 15-week-old spontaneously hypertensive rats (SHR) and DOCA-salt hypertensive rats were measured with a sandwich-type enzyme immunoassay. The vasocontractile effect of ET-1 in aortic helical preparations was significantly more sensitive in DOCA-salt hypertensive rats than in control sham-operated rats, but plasma levels of ET-1 did not differ between them. Plasma ET-1 levels in genetically hypertensive rats (SHR and stroke-prone SHR) were significantly lower than those in age-matched normotensive Wistar-Kyoto (WKY) rats. The plasma concentrations of big ET-1, a precursor of ET-1, in both SHR and SHR-SP were significantly lower than those of WKY, suggesting that the production of ET-1 is decreased in rats of genetic hypertension. Although the vascular reactivity to ET-1 increased in both DOCA-salt hypertensive and genetically hypertensive rats, present findings of the plasma ET-1 levels suggest that the role of ET-1 in the vascular control system may be different in DOCA-salt hypertensive rats and genetically hypertensive rats.