Morphometric evidence for non-pressure-related arterial wall thickening in hypertension

To investigate the relation of pressure and vascular wall thickening in hypertension, we coarcted the abdominal aorta upstream to the renal arteries in 14 rats. Sham-coarcted (n = 16) and two-kidney, one-clip (Goldblatt) hypertensive rats (n = 13) served as controls. Tail, femoral, and carotid arterial pressures rose (p less than 0.01) in the two-kidney, one-clip hypertensives; only carotid pressure rose (p less than 0.01) in the coarcted rats, tail and femoral pressures remaining normal (p greater than 0.25). Thus, the hindquarters of the coarcted rats remained normotensive. Four to six weeks after surgery we perfusion-fixed vascular tissues of the hindquarters, including kidneys, with formalin at in vivo levels of pressure. Glycol methacrylate-embedded tissues were sectioned at 1 micron thickness and vessels quantitatively evaluated. The outer medial and lumen perimeters of abdominal aorta, femoral artery, and renal arterioles were measured; from these measurements, vessel outer and lumen diameters, medial thickness, medial area, and medial thickness-to-lumen radius ratios were calculated. Compared with sham-coarcted rats, abdominal aorta, femoral arteries, and renal arterioles less than 61 microns outer diameter in rats with coarctation and Goldblatt hypertension had significantly increased (up to +100%) medial area, medial thickness, and medial thickness-to-lumen radius ratios. In general, magnitudes of abnormalities were similar in Goldblatt and coarcted rats. Renal arterioles greater than 60 microns outside diameter in Goldblatt hypertensive, but not coarcted, rats also were thickened. These results indicate that vascular wall thickening occurs in conduit arteries and smaller renal arterioles in the normotensive hindquarters of coarcted rats, providing morphometric evidence for non-pressure-related mechanisms involved in vascular growth in this form of hypertension.     

Aortic hypertrophy and "waterlogging" in the development of coarctation hypertension

To study the mechanisms and roles of vascular structural changes during the development of hypertension, we coarcted or sham-coarcted the abdominal aorta of rats. At intervals of 3 to 56 days later, we obtained standardized segments of thoracic and abdominal aortas for measurement of dry weight, water content, and amino acid content. Carotid arterial pressure was elevated by day 5 in coarcted rats and remained elevated. Femoral and tail arterial pressures remained normal. Cardiac ventricular weight and dry weight of the thoracic aorta, normalized for body weight, rose rapidly over 3-10 days in coarcted rats, remaining constant at 50-60% above levels in sham-coarcted rats thereafter. In contrast, water content of thoracic aorta in coarcted rats peaked at 123% of control values on day 7 (p less than 0.001), falling rapidly thereafter to levels about half of peak. Increments in dry weight and water content of the normotensive abdominal aortic segments were of far lesser magnitude and occurred 1 to 2 weeks later, probably reflecting the effects of initial hypotension of the hindquarters. Percent hydroxyproline of intima-media segments of the thoracic aorta remained normal during the 8-week period, indicating that increases in aortic dry weight did not represent disproportional fibrosis and thus are attributable to muscular hypertrophy. These results provide support for the hypothesis that arterial wall "waterlogging" is primarily an early manifestation of the hypertensive process. The greatest magnitude of waterlogging coincides with the rapid early increase in aortic dry weight, representing hypertrophy, which suggests common mechanisms, such as activation of Na+-H+ antiport.     

Increased resistance and impaired maximal vasodilation in normotensive vascular beds of rats with coarctation hypertension

To study the resistance of normotensive vascular beds in coarctation hypertension, we measured perfusion pressures of pump-perfused (blood), innervated, isolated hindlimbs of 12 rats (Group A) with 4 weeks of hypertension due to partial contriction of the abdominal aorta above the renal arteries, and of three control groups: 11 normotensive rats (Group B) with aorta sham-constricted, nine normotensive rats (Group C) with slight (5%) hindquarters atrophy due to partial constriction of the abdominal aorta below the renal arteries, and six rats with two-kidney, one clip Goldblatt hypertension (Group D). After aortic constriction, measured femoral arterial pressures in Group A rats remained normotensive. In hypertensive rats of Groups A and D, compared to normotensive Group B or C rats, hindlimb pressure-flow curves were displaced toward the pressure axis (p < 0.05). Compared to normotensive rats, drop in hindlimb resistance after acute local nerve section was increased in rats with coarctation hypertension. Residual resistance after maximal vasodilation with intraarterial sodium nitroprusside remained elevated in hypertensive rats of Groups A and D (p < 0.05), as compared to normotensive Group B or C rats; compared to Group B rats, this residual resistance in the coarcted rats of Group A was increased by 9%. Thus, in normotensive vascular beds of rats with chronic hypertension caused by aortic coarctation, resistance is elevated. The neurogenic component contributes to this high resistance, and structural vascular changes, indicated by impaired maximal vasodilation, may also contribute to the elevated resistance. It is most unlikely that these resistance changes are attributable to elevated hindlimb intravascular pressures.     

Analysis of changes in reactivity of rabbit arteries and veins two weeks after induction of hypertension by coarctation of the abdominal aorta.

Vessel dimensions and characteristic responses to norepinephrine were measured in various arteries and veins of the rabbit made hypertensive by partial constriction of the upper abdominal aorta. The ear, radial, and basilar arteries taken from the circulation proximal to the ligature (the hypertensive arteries) were thickened in proportion to the rise is arterial blood pressure. The water, sodium, and potassium contents of these and all other vessels were not significantly changed in the hypertensive rabbits. The maximum response to norepinephrine in the ear artery, a representative vessel from the hypertensive part of the rabbit, was increased, whhereas the sensitivity of this vessel to norepinephrine expressed as the ED50 did not alter with changes in the arterial blood pressure. In contrast, the thickness and the maximum response to norepinephrine of the saphenous artery, representative of vessels distal to the ligature (normotensive vessels) and of the saphenous and cephalic veins were unaltered. The sensitivity as indicated by the norepinephrine ED50 of the veins, but not of the saphenous artery, increased with a rise in carotid artery blood pressure. These results suggest that the increased responsiveness to norepinephrine of arteries proximal to the ligature is due to changes in muscle mass and that the increased responsiveness of the veins is due to increased sensitivity to norepinephrine.     

Transmission of hypertension in rats by cross circulation

Cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. Blood was pumped through two anastomoses between the carotid arteries and external jugular veins in both directions with equal flow rate. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9 +/- 12.2 mm Hg (p less than 0.01). Administration of digoxin antibody in a dose binding 0.25 mg digoxin to the spontaneously hypertensive rats before cross circulation prevented the transmission of hypertension to the normotensive rat, whereas chemical sympathectomy with 6-hydroxydopamine and intravenous injection of inactive Fab fragments had no inhibitory effect. It is concluded that, in this strain of spontaneously hypertensive rats, a circulating hypertensive factor exists. The factor binds to digoxin antibody and is not produced in sympathetic nervous tissue.     

Endothelium-dependent mechanical properties of the carotid artery in WKY and SHR. Role of angiotensin converting enzyme inhibition

An experimental model of in situ isolated carotid arteries has been used to evaluate the static mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The effects of endothelium removal and of local incubation with the converting enzyme inhibitor lisinopril (ICI Pharma 209000) on the carotid compliance (CC) were compared with the effects of total abolition of the vascular smooth muscle tone by potassium cyanide. CC measured for pressures ranging from 50 to 175 mm Hg had maximal values (0.22 +/- 0.07 microliter/mm Hg and 0.13 +/- 0.03 microliter/mm Hg, respectively, for WKY and SHR, p less than 0.001) for pressure values close to the operating pressures in both groups. Maximal values of CC were increased by 35% and 45% in WKY and SHR, respectively, after potassium cyanide poisoning (p less than 0.01). The endothelium removal induced a significant increase in CC compared with their control values (+37%, p less than 0.01, and +25%, p less than 0.01, respectively, in WKY and SHR). CC measured after endothelium removal did not significantly differ from its values measured after potassium cyanide poisoning in normotensive animals. In contrast, in hypertensive animals, CC was significantly lower after endothelium, removal than after potassium cyanide poisoning (p less than 0.01). In the presence of intact endothelium, local incubation with converting enzyme inhibitor increased CC by 23% (p less than 0.05) in WKY rats and by 14% (p less than 0.01) in SHR. In contrast, after endothelium removal, converting enzyme inhibitors did not significantly increase further CC in either strain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional and morphological pattern of vascular responses in two models of experimental hypertension

OBJECTIVES:

To determine the reactivity and accompanying structural changes in thoracic aorta and carotid artery from nitric oxide (NO)-deficient hypertensive and spontaneously hypertensive rats (SHR).

ANIMALS AND METHODS:

For the functional study, isolated rat arterial rings were precontracted with a submaximal concentration of phenylephrine (1 μM) and relaxant responses to cumulative concentrations of acetylcholine were obtained. For the morphological study, arteries were processed by a standard method for electron microscopy. The geometry of the arteries – the inner diameter and the wall thickness (tunica intima plus tunica media) – was evaluated by light microscopy.

RESULTS:

Increased systolic blood pressure was accompanied by increased heart weight to body weight ratio in both NO-deficient and SHR compared with normotensive controls, indicating cardiac hypertrophy. Morphometry of the thoracic aorta and carotid artery in both models of hypertension showed increased wall thickness, cross-sectional area and wall to diameter ratio. The inner diameter increased in aorta but not in carotid artery. In isolated arteries from normotensive rats, the addition of acetylcholine to precontracted vessels resulted in dose-dependent relaxation. The relaxing effect was more prominent in thoracic aorta than in carotid artery. Endothelium-dependent relaxation of arteries from NO-deficient hypertensive rats was markedly reduced. On the other hand, in aorta and carotid artery from SHR, the endothelium-dependent relaxation in response to acetylcholine was not significantly attenuated. The relaxation of arteries from SHRs, as well as the residual relaxation of arteries from NO-deficient hypertensive rats, was abolished by addition of N^G-nitro-l-arginine methyl ester, an inhibitor of NO synthase, to the incubation medium.

CONCLUSIONS:

These results suggest that increased systolic blood pressure and accompanying structural changes are not primarily responsible for impairment of endothelium-dependent relaxation in experimental hypertension.     

A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats

Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat. We studied the concentration of vascular kininogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212 +/- 4 mm Hg in the hypertensive rats (n = 33) and 120 +/- 1 mm Hg in the normotensive rats (n = 32) (p less than 0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56 +/- 8 versus 77 +/- 15), it was highly significant in the abdominal aorta (63 +/- 13 versus 167 +/- 17, p less than 0.001) and tail artery (48 +/- 8 versus 197 +/- 31, p less than 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183 +/- 16 versus 380 +/- 38, p less than 0.003), abdominal aorta (565 +/- 61 versus 1,093 +/- 74, p less than 0.001), and tail artery (532 +/- 112 versus 1,243 +/- 135, p less than 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213 +/- 56 versus 131 +/- 31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (1,803 +/- 221 versus 771 +/- 79, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular responsiveness to phorbol esters in coarctation-hypertensive rats

Recent observations suggest that a phospholipid-sensitive, calcium-dependent protein kinase affects the contractile responses of vascular smooth muscle. Protein kinase C activators such as the tumor-promoting phorbol esters have been used as tools to study protein kinase C function in various intact cells. The present study characterizes vascular reactivity to protein kinase C activation in rats made hypertensive by coarctation of the abdominal aorta. Thoracic aortic strips from hypertensive rats developed greater force than arteries from normotensive rats in response to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Thoracic aortae from hypertensive rats were more responsive (lower threshold dose) to the phorbol ester than those from normotensive rats. Additionally, arteries from hypertensive rats were more responsive to the contractile effects of mezerein, a non-phorbol ester activator of protein kinase C. Removal of the endothelium did not eliminate the difference in responsiveness to TPA in thoracic aortae from normotensive and hypertensive rats. The threshold dose of TPA in abdominal aortae from hypertensive rats was not different from that in normotensive rats. However, the maximal response to 10(-6) mol/l TPA after 60 min in abdominal aortae from hypertensive rats was significantly less than that in aortae from normotensive rats. Thus, contractile responses to TPA appear to be influenced by arterial pressure per se. The inhibitory effects of the calcium antagonist, verapamil, in thoracic aortae from hypertensive rats were greater than in those from normotensive rats. Verapamil inhibited TPA-induced contractions in abdominal aortae from hypertensive rats to the same extent as in those from normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo DNA synthesis is not uniformly increased in arterial smooth muscle of young spontaneously hypertensive rats.

We compared the distribution of DNA synthesis over the arterial tree of young normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with marginally elevated blood pressure. Six-week-old male SHR and WKY rats were therefore infused with 5-bromo-2'-deoxyuridine (BrdUrd) for 2 days and the nuclear incorporation of the thymidine analogue in the media of various arteries was determined by immunohistochemistry. In WKY rats, 2.5% of the arterial smooth muscle nuclei in elastic, muscular and resistance arteries incorporated BrdUrd. In SHR, DNA synthesis was more marked in large arteries than in resistance arteries. It was in addition significantly larger in the aorta, superior mesenteric, renal and femoral arteries of the SHR than in those of the WKY rats. However, nuclear incorporation of BrdUrd in vivo did not differ between SHR and WKY rats in aortic endothelium, carotid arterial smooth muscle, nor in mesenteric or renal resistance arteries. Between 6 and 20 weeks of age, the number of nuclear profiles per media cross-section did not increase in large arteries of WKY rats and SHR. During this period of time, however, carotid artery and thoracic aorta weight and DNA content increased. SHR large arteries gained more DNA than those of WKY rats. These data indicate that DNA synthesis is uniformly distributed over the arterial system in young WKY rats and that DNA synthesis is elevated in the smooth muscle of large arteries of 6-week-old SHR but not in their resistance arteries.     

Decreased water and potassium content in erythrocytes in essential hypertension

The water content in erythrocytes of subjects with borderline or established essential hypertension was measured by using gas-liquid chromatography and was found to be lower than that in normotensive controls (p less than 0.01). The water content in erythrocytes of normal controls (n = 14), borderline hypertensive subjects (n = 18), and established essential hypertensive subjects (n = 23) was (mean +/- SE) 71.0 +/- 0.2%, 69.9 +/- 0.2%, and 69.3 +/- 0.1% (vol/vol), respectively. A definite negative correlation was found between water content of erythrocytes and mean arterial pressure in normotensive and hypertensive subjects (n = 60, r = -0.59, p less than 0.001). Although there was no statistically significant between-group difference in the sodium content, the potassium content of erythrocytes from subjects with essential hypertension was significantly lower than that of normotensive controls (0.205 +/- 0.003 vs 0.222 +/- 0.004 mumol/mg dry red blood cells; p less than 0.01). There was no between-group correlation of sodium and water content in erythrocytes, but the potassium content correlated with the water content (n = 46, r = 0.49, p less than 0.001).     

Arteriolar wall thickening in hypertensive rats unrelated to pressure or sympathoadrenergic influences

We have previously reported that experimental aortic coarctation in rats is accompanied by non-pressure-related increases in the wall-to-lumen ratio (W/L) of cremaster arterioles. To investigate the role of the sympathoadrenergic system in this arteriolar wall thickening, we partially constricted or sham-constricted the abdominal aorta in adrenal-demedullated, 6-week-old rats that had had guanethidine injections to produce peripheral sympathectomy (S rats, n = 17 coarcted, 16 sham-coarcted) and in sham-demedullated, sham-sympathectomized control rats (SS rats, n = 13 coarcted, 15 sham-coarcted). In both SS and S rats with coarctation, tail and femoral arterial and conscious abdominal aortic pressures were not increased but carotid pressures rose by greater than 30% (p less than 0.01), accompanied by 46-75% increases in cardiac ventricular weight/body weight. In coarcted rats, 4-6 weeks after aortic constriction, compared with sham-coarcted rats, whether S or SS, observation of the cremaster microcirculation revealed increased wall area, wall thickness, and W/L of third- to fifth-order arterioles, both in the resting state and after maximal relaxation with topical nitroprusside. For example, in coarcted S rats wall area after nitroprusside was elevated by 24%, 39%, and 37% in third-, fourth-, and fifth-order arterioles (p less than 0.01). These findings indicate that arteriolar wall thickening in hypertension may occur independently of intra-arterial pressure or sympathoadrenergic influences. Humoral growth factors may be involved.     

Collagen I and III and mechanical properties of conduit arteries in rats with genetic hypertension

Conduit arteries of hypertensive rats are thicker and stiffer than those of normotensive controls. The possible role played by collagen type I and II subtypes in the mechanism of arterial stiffness remains unknown. The carotid and aortic arterial wall of rats of Japanese (Wistar-Kyoto and spontaneously hypertensive rats) and Lyon (normotensive and hypertensive rats) origin were studied. The stiffness of the carotid wall material (ultrasound), the histomorphometry of the aortic wall with the content in collagen I and III subtypes and their corresponding mRNA were analyzed. Independently of hypertension, the Japanese group differed from the Lyon group by a stiffer carotid wall material at any given value of wall stress; a lesser degree of aortic hypertrophy with a higher percentage of elastin, and a higher density of collagen III but not of collagen I. All other hemodynamic and histomorphometric parameters were affected by both the origin of the rats (Japanese vs. Lyon) and the presence of hypertension. Large artery stiffness in genetically hypertensive rats was not only influenced by hypertension itself, but also by differences in the contents of collagen subtypes which are also found in their corresponding normotensive controls.     

Altered structure and distensibility of arteries in salt-fed rats

BACKGROUND AND OBJECTIVES: Habitual high-sodium diet may cause stiffening of arteries. The aim of this study was to investigate the long-term effects of physiologically relevant high-sodium diet on the structure and distensibility of arteries in rats. METHODS: Adult male Sprague-Dawley rats were fed 2% NaCl diet for 3 or 6 months; rats fed 0.7% NaCl diet were controls. Pressure-volume (distensibility) relationships were measured in the presence and absence of calcium in excised, in-vitro perfused segments of right carotid artery and of second order mesenteric arteries. The left carotid artery and the remaining mesenteric arteries of rats were perfused in situ with papaverine followed by fixative at 100 mmHg, and then embedded in epoxy for morphometric measurements. RESULTS: The tail systolic blood pressure (SBP), and in subgroups of rats, the directly measured mean arterial pressure (MAP), of salt-fed rats at 3 and 6 months were unchanged. At 3 months, there was dilatation (increased lumen area) of both carotid and mesenteric arteries of salt-fed rats, without a change in distensibility. At 6 months, the lumen area of carotid arteries of salt-fed rats returned to control value (inward remodeling), and carotid artery distensibility remained unchanged. At 6 months, there was further dilatation (P <0.01) and reduced distensibility (P =0.01) of mesenteric arteries in salt-fed rats. CONCLUSIONS: A three-fold increase in dietary sodium intake leads to dilatation of arteries in normotensive rats. When there is compensatory remodeling, the distensibility of arteries remains unchanged; when compensation is lacking, unopposed dilatation is associated with reduced distensibility.     

Vascular angiotensin converting enzyme activity in spontaneously hypertensive rats and its inhibition with cilazapril

Angiotensin converting enzyme (ACE) activity was examined in large arteries and veins of rats and found to be present in most of the arteries and to a lesser extent in the veins, except for the femoral vessels which showed higher ACE activity in the vein than in the artery. For the aorta and all its branches, ACE activity was higher in the aorta and its branches in spontaneously hypertensive rats (SHR) than in age-matched normotensive Wistar-Kyoto rats (WKY), with the exception of the hepatic, pulmonary and basilar arteries where the levels were similar for SHR and WKY. For the vena cava and brachial vein, ACE activity was also higher in SHR than WKY but for most other veins the activity was the same with the exception of the pulmonary vein where ACE activity was higher in WKY. The acute treatment of SHR with cilazapril, an ACE inhibitor (0.3 and 3 mg/kg orally, for 4h) decreased aortic blood pressure and ACE activity in arterial and venous mesenteric and renal vessels in a dose-dependent fashion. Cilazapril, at the threshold hypotensive dose, markedly decreased ACE activity in each pair of aortic segments, carotid, pulmonary, subclavian, brachial and femoral vessels to a degree which was equivalent to that caused by the high dose. The effect outlasted a fall in blood pressure 24 h later. This was associated with a marked decrease in plasma angiotensin II and III and accumulation of angiotensin 1 at 4 h. No increase in plasma bradykinin or kallidin levels was detected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of insulin on renal sodium handling in hypertensive rats

Spontaneously hypertensive rats have reduced peripheral insulin sensitivity. To determine whether hypertensive rats demonstrate reduced response to the antinatriuretic effect of insulin, urinary sodium excretion was determined in hypertensive and normotensive rats (n = 7 per group) before and during euglycemic insulin administration at two infusion rates (21 milliunits/kg load and 4 milliunits/kg/min or 85 milliunits/kg load and 8 milliunits/kg/min). Hypertensive and normotensive time controls received the vehicle for insulin administration. Mean arterial pressure was greater (p less than 0.05) and inulin clearance was less (p less than 0.05) in hypertensive than normotensive rats before insulin infusion. Baseline fractional sodium excretion was not different between groups. Low dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.81 +/- 0.43% to 0.31 +/- 0.07% in hypertensive rats and from 1.05 +/- 0.37% to 0.47 +/- 0.18% in normotensive rats. High dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.67 +/- 0.22% to 0.21 +/- 0.08% in hypertensive rats and from 0.81 +/- 0.15% to 0.30 +/- 0.09% in normotensive rats. Sodium excretion was unchanged in time controls. The reduction in sodium excretion was similar in both rat groups during low dose and high dose insulin infusions. Mean arterial pressure and inulin clearance were unchanged from baseline values during insulin infusion in all rat groups. Glucose requirement to maintain euglycemia was greater (p less than 0.05) in normotensive than hypertensive rats at both insulin infusion rates. Thus, while hypertensive rats have reduced sensitivity to the hypoglycemic effects of insulin, the antinatriuretic response to insulin is not different from that of normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chronic heart rate reduction with ivabradine on carotid and aortic structure and function in normotensive and hypertensive rats

BACKGROUND: A reduction of heart rate (HR) by surgical means or pharmacological agents affects the progression and/or regression of atherosclerotic lesions. Nevertheless, the effect of bradycardia per se on large artery structure and function has never been investigated in rat models of hypertension. METHODS: Four groups of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were treated for 28 days either by placebo or by the selective HR-reducing agent ivabradine (8.4 mg/kg/day), a novel compound devoid of inotropic or vasodilating effects and without direct action on the autonomic nervous system. At the end of the follow-up period, intra-arterial blood pressure, carotid pulsatile arterial hemodynamics (echo tracking techniques) and the medial cross-sectional area (MCSA) of the aorta and the carotid artery were determined. RESULTS: In conscious animals, chronic administration of ivabradine significantly reduced HR by 26-30% with no change in tail systolic blood pressure. In anesthetized animals, the decrease in HR and the subsequent increase in the diastolic period were responsible for a decrease in diastolic blood pressure. At the site of the large arteries, ivabradine produced a decrease in the MCSA of the thoracic but not of the abdominal aorta, as well as an increase in pulsatile change of the carotid diameter without change in the isobaric distensibility and MCSA. The changes in pulsatile diameter were significantly larger in WKY rats than in SHRs. CONCLUSION: In normotensive and mainly in SHRs, selective chronic HR reduction by ivabradine is associated with alterations in large arteries involving an aortic antihypertrophic effect.     

300例高血压前期者脉搏波传导速度与颈动脉硬化改变及相关性

目的 探讨高血压前期人群大动脉顺应性和颈动脉硬化的情况及相关性.方法 分层随机抽取高血压前期、高血压、正常血压各300例作为研究对象.采用动脉硬化诊断装置VP-1000测定肱踝脉搏波传导速度和踝臂指数,多普勒彩色超声观察颈总动脉内膜-中膜厚度以及斑块形成情况,比较三组间差异.比较各血压组合并颈动脉斑块时脉搏波传导速度的变化情况,分析颈动脉内膜-中膜厚度与脉搏波传导速度的相关性.结果 (1)随着血压从正常向高血压转变,肱踝脉搏波传导速度呈上升趋势,高血压前期组(1 390±171 cm/s)较正常血压组(1 293±151 cm/s)升高但低于高血压组(1 652±291 cm/s,P<0.01);踝臂指数高血压前期组(1.115±0.060)与正常血压组(1.114±0.061)相比差异无统计学意义(P>0.05),但在高血压组明显升高(1.132±0.067,P<0.01).(2)颈动脉内膜-中膜厚度增厚率及斑块发生率在高血压前期组与正常血压组相比差异均无统计学意义,但在高血压组显著升高(P<0.01);颈总动脉内膜-中膜厚度在高血压前期组(0.73±0.10mm)与正常血压组(0.72±0.12 mm)相比差异无统计学意义(P>0.05),但在高血压组显著增厚(0.78±0.16 mm,P<0.01).(3)有或无合并颈动脉斑块时,高血压前期组脉搏波传导速度均较正常血压组升高(P<0.01),但低于高血压组(P<0.01);各血压组合并颈动脉斑块时脉搏波传导速度较无颈动脉斑块时均升高(P<0.01).肱踝脉搏波传导速度与颈总动脉内膜-中膜厚度呈正相关(r=0.271,P<0.01),校正血压因素后相关性仍存在(r=0.156,P<0.01).结论 高血压前期肱踝脉搏波传导速度显著升高.提示存在早期动脉硬度改变.肱踝脉搏波传导速度与颈动脉内膜-中膜厚度呈正相关,肱踝脉搏波传导速度可作为评估高血压前期动脉硬度有效且简便易行的指标.     

Intralymphocytic sodium and free calcium and plasma renin in essential hypertension

Intracellular sodium, potassium, and free calcium concentrations were investigated in lymphocytes of 30 patients with essential hypertension and 30 normotensive controls. All subjects were placed on a diet containing 8 to 10 g of sodium chloride per day. Lymphocyte sodium concentration was higher in hypertensive patients than in normotensive controls (19.8 +/- 1.8 vs 18.4 +/- 1.8 mmol/kg wet weight; p less than 0.01), whereas lymphocyte potassium concentration was similar in both groups. Lymphocyte free calcium concentration was also higher in hypertensive patients than in normotensive controls (134.6 +/- 13.2 vs 120.2 +/- 16.4 nmol/L; p less than 0.01). There was a positive correlation between lymphocyte sodium and free calcium concentrations in normotensive controls, in hypertensive patients, and in the subjects combined (r = 0.59, p less than 0.01; r = 0.71, p less than 0.001; and r = 0.70, p less than 0.001, respectively). Lymphocyte potassium concentration was not related to lymphocyte sodium or free calcium concentration in each group. In patients with essential hypertension, intracellular sodium and free calcium concentrations were negatively correlated with plasma renin activity (r = -0.66, p less than 0.001; r = -0.60, p less than 0.001, plasma norepinephrine concentration. These results suggest that a considerable relationship exists between intracellular sodium and free calcium in lymphocytes and that, in essential hypertension, the alteration in cellular metabolism of sodium and calcium may be linked to the renin system but not to blood pressure, age, or adrenergic activity.     

Calcium influx and vascular reactivity in systemic hypertension

Numerous studies have focused on functional vascular changes that characterize the hypertensive state. Recent evidence that suggests that increased vascular reactivity in hypertension is due to changes in the delivery of activator Ca++ through channels in the cell membrane will be reviewed. The primary evidence supporting this hypothesis comes from studies that characterize the effects of Ca++-free solution and calcium channel blockers on contractile properties of isolated vascular smooth muscle. In the present study, experiments were performed to investigate the role of Ca++ influx in vascular contractions produced by interventions that cause membrane depolarization. Isometric tension development in helical strips of carotid arteries from stroke-prone spontaneously hypertensive rats in response to elevated K+ and tetraethylammonium chloride was greater than that in carotid arteries from Wistar-Kyoto normotensive rats. The rate of tension development to K+-free solution in carotid arteries from stroke-prone spontaneously hypertensive rats was faster than in Wistar-Kyoto normotensive rat arteries. Contractile responses to all 3 depolarizing interventions were reduced in arterial strips incubated in Ca++-free solution containing the chelator ethylene glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid and in arterial strips treated with the Ca++ channel blocker verapamil. These results are consistent with the hypothesis that constrictor stimuli that produce membrane depolarization cause an opening of Ca++ channels in the plasma membrane that are sensitive to the organic channel blockers. Further, a change in Ca++ permeability or membrane depolarizing mechanisms contributes to increased contractile responsiveness in carotid arteries of stroke-prone spontaneously hypertensive rats.