Increased sympathetic innervation in the cerebral and mesenteric arteries of hypertensive rats

The density of catecholamine-containing nerve fibers was studied in the cerebral and mesenteric arteries from normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) in the growing (SHR, WKY) and adult (SHR, SHRSP, WKY) animals. Cerebral arteries from SHR showed an increased adrenergic innervation from day 1. The nerve plexuses reached an adult pattern earlier in SHR than in WKY. The arteries from adult SHR and SHRSP (22 weeks old) showed a markedly higher nerve density than WKY. There was a positive linear correlation between blood pressure and nerve density for four cerebral arteries. The mesenteric arteries were not innervated at birth. However, hyperinnervation of these arteries in the SHR was already present at 10 days of age as compared with WKY. Sympathectomy with anti-nerve growth factor and guanethidine caused a complete disappearance of fluorescent fibers in the mesenteric arteries from SHR and WKY, and in the cerebral arteries of WKY. The same procedure caused only partial denervation of the cerebral arteries from hypertensive animals. We postulate that the increase in nerve density in the cerebral arteries from the hypertensive rats may contribute to the development of arterial hypertrophy in chronic hypertension through the trophic effect of the sympathetic innervation on vascular structure.     

Specificity of the hemodynamic indices’ shift in SHR line rats at different age

Specificities of the changes in the systemic hemodynamics indices in the spontaneously hypertensive line SHR rats have been studied in comparison with the normotensive line WKY rats. It was demonstrated that an increase in blood pressure observed in the young hypertensive male rats, which have completed puberty (8 weeks old), is associated with the development of the hyperkinetic type arterial hypertension, which is characterized by increased cardiac minute output. It has been shown that SHR line male rats reveal the establishment of stable arterial hypertension due to a significant increase in the total peripheral resistance with the simultaneous recovery of the cardiac minute output by the 25th week of life. SHR line rats at the age of 15 weeks may be regarded as being in the period of transition from the hyperkinetic type arterial hypertension to stable arterial hypertension.     

Dietary sodium intake and age in spontaneously hypertensive rats: effects on blood pressure and sympathetic activity

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were placed on sodium restricted diets (9 and 17 mumol/g) or on a regular sodium diet (101 mumol/g) at 2, 4, 7, or 10 weeks of age, and continued until 16 weeks of age. Severe sodium restriction (9 mumol/g) initiated at 2 or 4 weeks of age prevented hypertension development in SHR and severely retarded growth. Hypertension development was attenuated when 9 mumol/g was initiated at 7 weeks of age, and was not affected when started at 10 weeks of age. Mean arterial pressure (MAP) in WKY receiving 9 mumol Na/g initiated at 2 and 4 weeks of age was below normal, but was not affected when this diet was given at 7 or 10 weeks of age. Less severe sodium restriction (17 mumol Na/g) resulted in a reduction in hypertension development when initiated at 2, 4, and 7 weeks of age, but not at 10 weeks of age. MAP was normal in WKY receiving 17 mumol Na/g at all ages of diet initiation. When the 9 or 17 mumol Na/g diet were initiated at 2, 4, and 7 weeks of age, the response of blood pressure to hexamethonium administration was blunted in SHR relative to both WKY receiving the same diet, and to control SHR receiving 101 mumol Na/g. We conclude that both WKY and SHR require a minimum amount of dietary sodium for normal growth and for the achievement of normal BP in WKY, and hypertension in SHR. This sodium requirement decreases with age. SHR and WKY exhibit similar sensitivities to sodium intake with respect to body weight, but the effects on BP are more pronounced in SHR. The BP lowering effects of dietary sodium restriction may be due to a blunting of the pressor effectiveness of the sympathetic nervous system.     

Arterial hypertension exacerbates oxidative stress in early diabetic retinopathy

The present study was undertaken to investigate the redox status in the retina of an experimental model that combines hypertension and diabetes. Spontaneously hypertensive rats (SHR) and their control Wystar Kyoto (WKY) rats were rendered diabetic and, after 20 days, the rats were sacrificed and the retinas collected. The superoxide production was higher in diabetic than in control WKY (p < 0.03) and SHR rats showed elevated superoxide production compared with WKY groups (p < 0.009). The glutathione antioxidant system was diminished only in diabetic SHR (p < 0.04). Tirosyne nitration was higher in diabetic WKY and control SHR compared with control WKY (p < 0.03), and further increment was observed in diabetic SHR (p < 0.02). The DNA damage estimated by immunohystochemistry for 8-OHdG was higher in control SHR than in WKY, mainly in diabetic SHR (p < 0.0001). Hypertension aggravates oxidative-induced cytotoxicity in diabetic retina due to increasing of superoxide production and impairment of antioxidative system.     

Inhibition of neurons in commissural nucleus of solitary tract reduces sympathetic nerve activity in SHR

Neurons in the commissural nucleus of the solitary tract (commNTS) play an important role in certain cardiovascular responses dependent on sympathetic vasoconstrictor activation, including the arterial chemoreceptor reflex. Electrolytic lesions of the commNTS elicit a fall in arterial pressure (AP) in spontaneously hypertensive rats (SHR). To determine whether the latter result 1) arose from elimination of commNTS neuronal activity rather than en passant axons and 2) was accompanied by a reduction in sympathetic nerve activity, we evaluated the effect of inhibition of neurons in the commNTS on basal splanchnic sympathetic nerve activity (SNA), AP, and heart rate (HR) in SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. In chloralose-anesthetized, paralyzed, and artificially ventilated SHR, microinjection of GABA into the commNTS markedly decreased splanchnic SNA, AP, and HR. The reductions in SNA and AP following similar microinjections in WKY and SD rats were significantly less than those in SHR. Our findings suggest that tonically active neurons in the commNTS contribute to the maintenance of SNA and the hypertension in SHR. The level of tonic discharge of these commNTS neurons in normotensive WKY and SD rats may be lower than in SHR.     

Hippocampal levels of dynorphin A (1–8) in neonatal and 16-week-old spontaneously hypertensive rats: Comparisons with DOCA-salt hypertension

In this study the possible role of hippocampal dynorphin in the development of hypertension in spontaneously hypertensive rats (SHR) was investigated by determining dynorphin A (1–8) (DN A (1–8)) levels in hippocampus in 16 week old SRH, Wistar Kyoto (WKY) controls and SHR treated with antihypertensive drugs as well as DOCA-salt hypertensive Sprague Dawley (SD) rats, using radioimmunoassay (RIA). We found that DN A (1–8) was decreased significantly in both dorsal (–68%) and ventral (–58%) hippocampus in SHR compared with WKY rats. Treatment with hydralazine and guanethidine (25 mg/kg/24 hr of each drug in drinking water) for 8 weeks to prevent the development of hypertension in young SHR had no effect on this low hippocampal dynorphin level. We failed to find significant changes in hippocampal DN A (1–8) level in DOCA-salt hypertensive rats. The low level of hippocampal dynorphin existed before the development of hypertension in 6 day neonatal SHR (–73%). Hippocampal Met-enkephalin was unchanged in all experimental groups except for a slight decrease in neonatal SHR. The results establish a genetic difference in the hippocampal dynorphin system of SHR compared with WKY, the significance of which, for the development of hypertension, remains to be investigated.     

Role of Ca2+/calmodulin-dependent protein kinase II in development of vascular dysfunction in diabetic rats with hypertension

We examined the influence of chronic treatment with KN-93 (an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), 5 mg/kg given every other day for 4 weeks) on mean arterial pressure (MAP), urine protein and vascular reactivity in streptozotocin (STZ)-induced diabetes in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Treatment with KN-93 did not cause any significant changes in body weight, blood glucose or MAP in any of the groups studied. However, diabetes-induced elevations in urine volume and protein were significantly attenuated in KN-93-treated animals. KN-93-mediated decrease in urine volume and protein was more pronounced in SHR compared to WKY rats. The increased vascular responsiveness to endothelin-1 and angiotensin II in isolated carotid arteries from STZ-treated WKY (D-WKY) and SHR (D-SHR) was normalized by chronic treatment with KN-93. Furthermore, chronic treatment with KN-93 significantly prevented the development of diabetes-induced endothelial dysfunction as impaired endothelium-mediated vascular relaxation to carbachol and histamine under diabetic conditions was reversed by parallel treatment with the inhibitor. These results suggest that signal transduction involving CaMKII contributes to the development of abnormal vascular reactivity and renal dysfunction during simultaneous occurrence of hypertension and diabetes. We conclude that inhibition of CaMKII-mediated signalling could be an effective way to antagonize the elevated activities of injury-promoting factors in diabetic patients with hypertension.     

Spontaneous hypertension is primarily the result of sympathetic overactivity and immunologic dysfunction

Overactivity of the sympathetic nervous system and immunologic dysfunction have been shown to contribute to development and maintenance of hypertension in the Okamoto spontaneously hypertensive rat (SHR). In this study, the combined effects of reduction in sympathetic activity and immunologic manipulation on spontaneous hypertension have been determined. Neonatal SHRs received sham implants or implants of thymic tissue from Wistar donor rats. In addition, the thymus-implanted SHRs underwent bilateral renal denervation when they were 6 weeks old. At the same time, the sham-implanted SHRs underwent sham renal denervation. The denervations or sham operations were repeated when the SHRs were 9, 12, 15, and 18 weeks old. Wistar-Kyoto (WKY) rats also underwent serial sham renal denervations. Tail-cuff pressure measurements indicated that approximately 75% of the chronic hypertension in the SHRs was prevented by the combination of thymic implants and renal denervations. Direct arterial pressure measurements confirmed these results; when the rats were 21 weeks old, mean arterial pressure averaged 177 +/- 5.5 mm Hg in sham-operated SHRs, 134 +/- 2.7 mm Hg in implanted, denervated SHRs, and 121 +/- 2.1 mm Hg in sham-operated WKY rats. These data indicate that overactivity of the sympathetic nervous system and immunologic dysfunction account for the majority of the hypertension in the Okamoto SHR.     

Sleep-related sympathovagal imbalance in SHR

The role of the autonomic nervous system in spontaneous hypertension during each stage of the sleep-wake cycle remains unclear. The present study attempted to evaluate the differences in cardiac autonomic modulations among spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD) across sleep-wake cycles. Continuous power spectral analysis of electroencephalogram, electromyogram, and heart rate variability was performed in unanesthetized free moving rats during daytime sleep. Frequency-domain analysis of the stationary R-R intervals (RR) was performed to quantify the high-frequency power (HF), low-frequency power (LF)-to-HF ratio (LF/HF), and normalized LF (LF%) of heart rate variability. WKY and SD had similar mean arterial pressure, which is significantly lower than that of SHR during active waking, quiet sleep, and paradoxical sleep. Compared with WKY and SD, SHR had lower HF but similar RR, LF/HF, and LF% during active waking. During quiet sleep, SHR developed higher LF/HF and LF% in addition to lower HF. SHR ultimately exhibited significantly lower RR accompanied with higher LF/HF and LF% and lower HF during paradoxical sleep compared with WKY. We concluded that significant cardiac sympathovagal imbalance with an increased sympathetic modulation occurred in SHR during sleep, although it was less evident during waking.     

Arterial hypertension exacerbates oxidative stress in early diabetic retinopathy

The present study was undertaken to investigate the redox status in the retina of an experimental model that combines hypertension and diabetes. Spontaneously hypertensive rats (SHR) and their control Wystar Kyoto (WKY) rats were rendered diabetic and, after 20 days, the rats were sacrificed and the retinas collected. The superoxide production was higher in diabetic than in control WKY (p<0.03) and SHR rats showed elevated superoxide production compared with WKY groups (p<0.009). The glutathione antioxidant system was diminished only in diabetic SHR (p<0.04). Tirosyne nitration was higher in diabetic WKY and control SHR compared with control WKY (p<0.03), and further increment was observed in diabetic SHR (p<0.02). The DNA damage estimated by immunohystochemistry for 8-OHdG was higher in control SHR than in WKY, mainly in diabetic SHR (p<0.0001). Hypertension aggravates oxidative-induced cytotoxicity in diabetic retina due to increasing of superoxide production and impairment of antioxidative system.     

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.     

糖尿病高血压大鼠动物模型的制备及稳定性观察

目的：探讨建立高血压合并糖尿病（DiabetesMellitus,DM）大鼠模型的方法,并观察模型的稳定性。方法：采用链脲佐菌素（Streptozotocin,STZ）腹腔注射的方法造模。8周龄的SHR大鼠（spontaneouslyhypertensiverats）16只,随机等分成对照组和造模组。另选8只8周龄WKY大鼠作为正常血压对照组。给予造模组SHR按55mg/kg体重的剂量腹腔注射STZ,诱导建立糖尿病高血压大鼠动物模型。结果：小剂量STZ（55mg/kg）腹腔注射SHR制备的糖尿病高血压大鼠模型,造模成本低,成模率高,模型稳定。结论：造模组能成功诱导建立糖尿病高血压大鼠模型。     

Studies of arterial smooth muscle relaxation in younger (16-18 week) and older (28-31 week) spontaneously hypertensive rats

Both isometric and isotonic relaxation rates have previously been reported to be decreased in caudal arterial and mesenteric resistance arterial smooth muscle from 16- to 21-week-old spontaneously hypertensive rats (SHR) compared with muscle from age-matched normotensive Wistar-Kyoto rats (WKY). An increased maximum velocity of shortening (Vmax) and an increased shortening ability (delta Lmax) have also been reported for arterial smooth muscle from 16- to 21-week-old SHR. It has been suggested that both increased narrowing and prolonged narrowing of arteries contribute to the development of hypertension. However, SHR Vmax is not different from WKY Vmax when studying arterial muscle from older (28- to 31-week-old) rats. Thus increased arterial narrowing ability cannot be a contributing factor to the maintenance of hypertension. In this study the role of relaxation rate in the maintenance of hypertension was examined by comparing the relaxation rates of isometric and isotonic contractions of caudal arterial strips from 16- to 21-week-old SHR (n = 9) and WKY (n = 8) and from 28- to 31-week-old SHR (n = 7) and WKY (n = 5). While relaxation rates were lower for 16- to 21-week-old SHR compared with age-matched WKY preparations for both isometric and isotonic contractions, only isometric relaxation rates were found to be different in 28- to 31-week-old SHR compared with 28- to 31-week-old caudal arterial muscle (p less than 0.05). Vmax tended to normalize from a once-elevated velocity, while isometric relaxation rate remained decreased in SHR with ageing and (or) with progression of the hypertensive condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats

The sympathetic nervous system and renin-angiotensin system are both thought to contribute to the development and maintenance of hypertension in experimental models such as the spontaneously hypertensive rat (SHR). We demonstrated that periarterial nerve stimulation (NS) increased the perfusion pressure (PP) and neuropeptide Y (NPY) overflow from perfused mesenteric arterial beds of SHRs at 4-6, 10-12, and 18-20 wk of age, which correspond to prehypertensive, developing hypertensive, and maintained hypertensive stages, respectively, in the SHR. NS also increased PP and NPY overflow from mesenteric beds of Wistar-Kyoto (WKY) normotensive rats. NS-induced increases in PP and NPY were greater in vessels obtained from SHRs of all three ages compared with WKY rats. ANG II produced a greater increase in PP in preparations taken from SHRs than WKY rats. ANG II also resulted in a greater increase in basal NPY overflow from 10- to 12-wk-old and 18- to 20-wk-old SHRs than age-matched WKY rats. ANG II enhanced the NS-induced overflow of NPY from SHR preparations more than WKY controls at all ages studied. The enhancement of NS-induced NPY overflow by ANG II was blocked by the AT1 receptor antagonist EMD-66684 and the angiotensin type 2 receptor antagonist PD-123319. In contrast, ANG II greatly enhanced norepinephrine overflow in the presence of PD-123319. Both captopril and EMD-66684 decreased neurotransmitter overflow from SHR mesenteric beds; therefore, we conclude that an endogenous renin-angiotensin system is active in this preparation. It is concluded that the ANG II-induced enhancement of sympathetic nerve stimulation may contribute to the development and maintenance of hypertension in the SHR.     

Prolonged isobaric relaxation time in small mesenteric arteries of the spontaneously hypertensive rat

Prolonged isometric relaxation in hypertensive aortic and caudal arterial smooth muscle has been demonstrated; however, isobaric relaxation in resistance arteries is more pertinent to studies in hypertension. A comparative study of mesenteric arterial isobaric relaxation times was made using spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and MK-421 treated SHR (treatment commenced at 8 weeks of age and was maintained until sacrifice). Relaxation rates of vessels constricting against a range of pressures and achieving different degrees of narrowing or changes in circumference were analyzed. Comparisons were made between SHR, WKY, and MK-421 treated SHR arteries that had constricted from the same initial circumference and against the same magnitude of pressure. The SHR mesenteric arteries relaxed at a slower rate than did the WKY vessels. The normotensive MK-421 treated SHR showed the same prolonged relaxation rate as did the untreated SHR preparations. Thus the slower rate of relaxation in SHR arteries does not appear to be a consequence of the hypertension. Such prolonged time for narrowing would function to increase the average peripheral resistance and thus may contribute to the initiation and maintenance of increased blood pressure.     

The antihypertensive effect of ethylcholine aziridinium (AF64A), a cholinergic neurotoxin, in spontaneously hypertensive rats, following administration into the posterior hypothalamus

The aim of this study was to ascertain whether drug-induced cholinergic hypofunction in the posterior hypothalamus would affect the development and the maintenance of hypertension in hypertensive rats. Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were treated with AF64A, a neurotoxin which can irreversibly inhibit cholinergic transmission in vivo. AF64A or saline was injected bilaterally into the posterior hypothalamus of rats of two age groups: normotensive one month-old rats whose blood pressure was subsequently measured at the age of three months and hypertensive three month-old rats, whose blood pressure was measured four weeks later. In both age groups there was a significant fall in mean arterial blood pressure in SHR but not WKY rats. In SHR injected at the age of one month, there was a fall of at least 15.9 mm Hg, while in the rats injected at the age of three months there was a fall of 14.3 mm Hg. Heart rate in either strain was not affected. When AF64A was injected into the anterior hypothalamus of one month-old SHR, no antihypertensive effect was observed in these rats at the age of three months. These results show that cholinergic stimulation in the posterior hypothalamus may play a role in both the development and maintenance of hypertension in SHR.     

Dietary sodium restriction and blood pressure response to sympathetic blockade in young versus adolescent spontaneously hypertensive rats

The effects of dietary sodium restriction on the maintenance of blood pressure (BP) by sympathetic tone were evaluated in young versus more mature spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Sympathetic activity was assessed by BP responses to alpha 1-receptor blockade (prazosin), central inhibition of sympathetic outflow (clonidine), and by ganglionic blockade (hexamethonium). On regular sodium intake, SHR showed elevated BP and increased BP responses to sympathetic blockade at both 10 and 16 weeks of age. Sodium restriction to 9 or 17 mumols Na+/g food prevented or blunted development of hypertension in SHR when started at 4 weeks of age but did not affect BP when started at 10 weeks of age. Sodium restriction initiated in young SHR also prevented development of increased BP responses to sympathetic blockade. However, sodium restriction in more mature SHR did not decrease the increased BP responses to sympathetic blockade. We conclude that prevention of development of sympathetic hyperactivity in young SHR represents a major mechanism in the antihypertensive effect of sodium restriction in young SHR.     

Myocardial fibrosis, impaired coronary hemodynamics, and biventricular dysfunction in salt-loaded SHR

Arterial pressure in most experimental and clinical hypertensions is exacerbated by salt. The effects of salt excess on right and left ventricular (RV and LV, respectively) functions and their respective coronary vasodilatory responses have been less explored. We therefore examined the effects of 8 wk of NaCl excess (8% in food) on arterial pressure, RV and LV functions (maximal rate of increase and decrease of ventricular pressure; dP/dt(max) and dP/dt(min)), coronary hemodynamics (microspheres), and collagen content (hydroxyproline assay and collagen volume fraction) in young adult normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), aged 16 wk by the end of the study. Prolonged salt excess in WKY and SHR elevated pressure only modestly, but it markedly increased LV mass, especially in SHR. Moreover, salt excess significantly impaired RV and LV diastolic function in SHR but only LV diastolic function in WKY rats. However, salt loading affected neither RV nor LV contractile function in both strains. Interstitial and perivascular collagen deposition was increased, whereas coronary vasodilatory responses to dipyridamole diminished in both ventricles in the salt-loaded SHR but not in WKY rats. Therefore, accumulation of ventricular collagen as well as altered myocardial perfusion importantly contributed to the development of salt-related RV and LV dysfunctions in this model of naturally occurring hypertension. The unique effects of salt loading on both ventricles in SHR, but not WKY rats, strongly suggest that nonhemodynamic mechanisms in hypertensive disease participate pathophysiologically with salt-loading hypertension. These findings point to the conclusion that the concept of "salt sensitivity" in hypertension is far more complex than simply its effects on arterial pressure or the LV.     

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     

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。