摘要:

The goal of this study was to examine the hypothesis that increases in pulse pressure produce hypertrophy of cerebral arterioles, even in the absence of increases in mean pressure. Sprague-Dawley rats underwent creation of an arteriovenous fistula and clipping of one carotid artery at 1 month of age. Rats that underwent exposure of the abdominal aorta without fistula production and unilateral carotid clipping served as controls. At about 6 months of age, the mechanics of sham and clipped pial arterioles were examined in vivo in anesthetized rats. Stress-strain relations were calculated from measurements of pial arteriolar pressure (servo null) and diameter and cross-sectional area of the arteriolar wall. Point counting stereology was used to quantify individual components in the arteriolar wall. Before deactivation of smooth muscle with EDTA, cross-sectional areas of the vessel wall and pulse pressures in sham pial arterioles were significantly greater (P < .05) in arteriovenous fistula rats than in control rats (cross-sectional area, 1468 plus/minus 100 versus 1129 plus/minus 104 micro meter2; pulse pressure, 26 plus/minus 1 versus 14 plus/minus 1 mm Hg). In contrast, systolic and mean pressures in sham arterioles were not significantly different and diastolic pressure was significantly less in arteriovenous fistula rats (systolic pressure, 69 plus/minus 1 versus 67 plus/minus 4 mm Hg; mean pressure, 52 plus/minus 2 versus 57 plus/minus 3 mm Hg; diastolic pressure, 43 plus/minus 2 versus 53 plus/minus 3 mm Hg). Carotid clipping normalized cross-sectional area of the vessel wall (1083 plus/minus 86 micro meter2) and pulse pressure (12 plus/minus 1 mm Hg) in pial arterioles of arteriovenous fistula rats. During maximal dilatation, the stress-strain curve in sham arterioles of arteriovenous fistula rats was shifted to the right of the curve in control rats, which indicates that arteriovenous fistulae increase passive distensibility of cerebral arterioles. The proportion of distensible components in the vessel wall (smooth muscle, elastin, and endothelium) was increased in sham arterioles of arteriovenous fistula rats. These findings (1) suggest that increases in pulse pressure, even in the absence of increases in mean pressure, are sufficient to produce hypertrophy of cerebral arterioles and (2) provide support for the concept that increases in distensibility of cerebral arterioles in association with hypertrophy of the vessel wall may be related to alterations in wall composition. (Hypertension. 1996;27:159-167.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Our objective was to validate a carotid artery tonometry-derived augmentation index as a means to estimate augmentation index (AI) of ascending aortic pressure under various physiological conditions. A total of 66 patients (50 men, 16 women; mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the Unites States) undergoing diagnostic catheterization were studied. Arterial pressure contours were obtained simultaneously from the right common carotid artery by applanation tonometry with an external micromanometer-tipped probe and from the ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The AI (expressed as percentage values) was calculated as the ratio of amplitude of the pressure wave above its systolic shoulder to the total pulse pressure. The carotid AI was consistently lower than the aortic AI, but the two were highly correlated at baseline and after both handgrip and nitroglycerin. Mean plus/minus SD and correlation coefficients were baseline (14 plus/minus 16, 28+plus/minus 17, .77), handgrip (18 plus/minus 19, 32+plus/minus 15, .86), and nitroglycerin (7 plus/minus 12, 18+plus/minus 13, .52). In addition, after adjusting for age, sex, height, blood pressure, heart rate, and study site, the changes of both Als from baseline values with handgrip or nitroglycerin were highly associated such that the aortic AI could be approximated from the carotid AI with appropriate regression equations. The high correlations and predictable changes after interventions between the central AI and those estimated from noninvasive carotid tonometry suggest that this technique may have wide applicability for many cardiovascular studies. (Hypertension. 1996;27:168-175.).

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Chronic nitric oxide inhibition exacerbates hypertension and nephrosclerosis in spontaneously hypertensive rats (SHRs). In this study, we determined whether angiotensin-converting enzyme (ACE) inhibition could prevent or reverse the systemic, renal, and glomerular hemodynamic alterations and the pathological changes of nephrosclerosis. Four groups of 20-week-old SHRs were studied: group 1, untreated controls; group 2, treated with Nomega-nitro-L-arginine methyl ester (L-NAME, 50 mg/L for 3 weeks); group 3, L-NAME cotreated with quinapril (3 mg [centered dot] kg-1[centered dot] d-1for 3 weeks); and group 4, L-NAME for 3 weeks followed by quinapril for 3 weeks (same doses). The results of this study demonstrated that both cotreatment (group 3) and posttreatment (group 4) with quinapril reduced mean arterial pressure (186 plus/minus 9 and 192 plus/minus 9 mm Hg, respectively, compared with group 2 SHRs, 221 plus/minus 5 mm Hg) and total peripheral resistance index associated with significant reductions in afferent and efferent arteriolar resistances; nephrosclerosis pathological scores; and urinary protein excretion (all at least P < .01). ACE inhibition also significantly increased stroke index, single-nephron glomerular filtration rate, and ultrafiltration coefficient compared with the L-NAME SHRs. Most notable were the findings that cotreatment with quinapril completely prevented the renal glomerular hemodynamic alterations with reduced glomerular capillary hydrostatic pressure and efferent arteriolar resistance compared with both the untreated and the L-NAME-treated SHRs (all at least P < .01). Posttreatment with quinapril also reversed the glomerular injury (subcapsular, -83%; juxtamedullary, -56%) and arteriolar (-87%) injury scores obtained from renal biopsy specimens (P < .005 and P < .0001, respectively). These changes were associated with decreased periarteriolar fibronectin and increased afferent arteriolar alpha-smooth muscle actin deposition (immunohistochemistry). These data, therefore, demonstrate that ACE inhibition not only prevents but also reverses L-NAME-exacerbated severe nephrosclerosis in SHRs, as indicated by improved systemic, renal, and glomerular hemodynamic changes, proteinuria, and histological alterations. (Hypertension. 1996;27:176-183.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In this study we examined whether L-arginine treatment could prevent corticotropin (ACTH)-induced increases in blood pressure in the Sprague-Dawley rat. Sixty rats were randomly divided into six groups (n = 10): sham injection, ACTH injection (0.5 mg/kg per day in divided doses), L-arginine (0.6%) in food plus sham injection, L-arginine plus ACTH treatment, D-arginine (0.6%) in food plus sham injection, and D-arginine plus ACTH. Systolic pressure, water intake, urine volume, body weight, plasma and urinary electrolytes, and serum corticosterone concentrations were measured. ACTH increased systolic pressure (from 127 plus/minus 2 to 165 plus/minus 6 mm Hg, P < .001), water intake, and urine volume and decreased body weight. L-Arginine reduced ACTH-induced blood pressure rises (130 plus/minus 3 mm Hg, P < .001) but had no effect on blood pressure in sham-treated rats. D-Arginine did not affect blood pressure in sham-treated rats, and systolic pressure in D-arginine + ACTH-treated rats was similar to that of ACTH-treated rats. L-Arginine decreased serum corticosterone concentrations in sham-treated rats (424 plus/minus 43 versus 238 plus/minus 25 ng/mL, P < .01), but D-arginine had no effect. However, both drugs decreased serum corticosterone concentrations in ACTH-treated rats (1071 plus/minus 117 versus 739 plus/minus 95 and 695 plus/minus 72 ng/mL for L- and D-arginine, respectively; both P < .05). As L-arginine but not D-arginine prevented ACTH-induced increases in blood pressure in Sprague-Dawley rats and both L- and D-arginine reduced serum corticosterone concentrations in ACTH-treated rats, the effects of L-arginine in preventing ACTH-induced hypertension were not simply a consequence of decreased corticosterone secretion. (Hypertension. 1996;27:184-189.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Glucocorticoids raise blood pressure but were thought not to play a pathophysiological role in essential hypertension when it was demonstrated that cortisol secretion rates and circulating concentrations are normal in this disease. However, recent observations suggest that increased tissue sensitivity to cortisol, mediated by either abnormal glucocorticoid receptors or impaired inactivation of cortisol by 11 beta-dehydrogenase, may allow cortisol to raise blood pressure despite normal circulating concentrations. We studied 11 patients with essential hypertension and 11 matched normotensive control subjects. Dermal vasoconstriction after topical application of both cortisol (16 plus and minus 4 versus 32 plus/minus 5 U, control subjects versus hypertensive patients; P < .02) and beclomethasone dipropionate (75 plus/minus 10 versus 100 plus/minus 7 U; P < .05) was increased in the hypertensive patients. Hypothalamic-pituitary glucocorticoid receptor sensitivity was normal, as judged by basal cortisol secretion rates and suppression of plasma cortisol during sequential overnight dexamethasone suppression tests. 11 beta-Dehydrogenase activity was impaired in essential hypertension, as judged by prolonged half-lives of [11 alpha-3Hydrogen]cortisol (44 plus/minus 4 versus 58 plus/minus 4 minutes, control subjects versus hypertensive patients; P < .02). However, this did not correlate with the dermal vasoconstrictor response. We conclude that vasoconstrictor sensitivity to glucocorticoids is increased in essential hypertension and that this may initiate and/or sustain the increased peripheral vascular resistance that characterizes this disease. The mechanism of increased sensitivity remains uncertain, but it will be important to establish whether it relates to genetic abnormalities of the glucocorticoid receptor that have been observed in animal models and young individuals who are predisposed to essential hypertension. (Hypertension. 1996;27:190-196.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and is important in blood pressure control. The excretion of renal 11 beta-HSD (ie, NAD+-dependent isoform) is thought to protect renal mineralocorticoid receptors from cortisol. To examine whether endogenous renal 11 beta-HSD inhibitory factor(s) may be involved in the pathophysiology of hypertension, we studied the urinary excretion of such inhibitors in 30 patients with low-renin essential hypertension and 20 normotensive control subjects. The effect of sodium restriction on the urinary excretion of the inhibitors was also evaluated in six normotensive control subjects. Urine was extracted with Sep-Pak cartridges and high-performance liquid chromatography. Endogenous renal 11 beta-HSD inhibitors were measured by the inhibition of 11 beta-HSD bioactivity in microsomes from the human kidney.

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Many patients with essential hypertension respond to a high dietary sodium intake with a rise in blood pressure. Experimental evidence suggests that the renal hemodynamic response to sodium determines, at least partially, this rise in blood pressure. Our aim was to clarify the role of the renin-angiotensin system in the renal and systemic adaptation to a change in dietary sodium. We studied changes in mean arterial pressure (MAP) (millimeters of mercury), effective renal plasma flow (ERPF), body weight, and immunoreactive renin in 17 patients with essential hypertension and 15 normotensive control subjects, randomly crossing over between a 3-week sodium-restricted (50 mmol/24 h) and a sodium-replete (200 mmol/24 h) diet period. In addition, the effects of renin inhibition by remikiren (600 mg, single oral dose) were studied during the high sodium period. In normotensive control subjects, high sodium intake had no effect on MAP or body weight, whereas ERPF increased (490 plus/minus 19 to 535 plus/minus 21 mL/min, P < .05) and immunoreactive renin decreased (32 plus/minus 6 to 14 plus/minus 1 pg/mL). In hypertensive subjects, high sodium intake induced a heterogeneous response of MAP (median change, 2.6 mm Hg; range, -4.7 to +21.2; P = NS) and ERPF (median change, 21 mL/min; range, -33 to +98; P = NS). Body weight increased from 81.3 plus/minus 1.9 to 82.5 plus/minus 2.0 kg (P < .05), and immunoreactive renin decreased from 18 plus/minus 3 to 10 plus/minus 1 pg/mL (P < .05). Interestingly, the patients with a distinct rise in MAP showed a blunted ERPF response to high sodium intake (r = -.70, P < .01) and an increase in body weight (r = .76, P < .001). Moreover, the increase of ERPF was more pronounced in patients with a larger fall in immunoreactive renin (r = .77, P < .001). After administration of remikiren, a heterogeneous response in ERPF was observed: the patients with the blunted ERPF response to high sodium intake showed the largest ERPF rise (r = .70, P < .01). The remikiren-induced rise in ERPF correlated (r = .68, P < .01) with the fall in MAP (114 plus/minus 2 to 110 plus/minus 2 mm Hg). In conclusion, in patients with essential hypertension a rise in blood pressure in response to high sodium intake appears to partially be the result of insufficient renal vasodilation. This seems to be due to an inadequate (intrarenal?) renin-angiotensin system response to increased sodium intake. (Hypertension. 1996;27:202-208.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Along with arterial blood pressure reduction, maintenance of the integrity of baroreceptor reflex function contributes to preserving end-organ function in the treatment of hypertensive patients. The purpose of this study was to investigate the effects of antihypertensive agents (trichlorme-thiazide, atenolol, nicardipine, and enalapril) on baroreceptor reflex function by comparing early and late starts of treatment. We administered each agent to spontaneously hypertensive rats (SHR) as early-start groups from 10 to 36 weeks of age and as late-start groups from 28 to 36 weeks of age. We evaluated the gain of the reflex control of renal sympathetic nerve activity and heart rate using ramp infusions of phenylephrine and nitroglycerin in untreated SHR at 10, 28, or 36 weeks of age and in treated SHR at 36 weeks of age. In 28- and 36-week-old untreated SHR, the renal sympathetic nerve activity gain was not altered and the heart rate gain was decreased (from -2.3 plus/minus 0.3 to -1.3 plus/minus 0.3 and -1.2 plus/minus 0.3 beats per minute [bpm]/mm Hg, P < .05, respectively) compared with 10-week-old SHR. Early and late start of therapy produced arterial pressure reductions (-18 plus/minus 4 and -12 plus/minus 5 mm Hg, P < .05, respectively). In the early-start groups, the renal sympathetic nerve activity gain was improved markedly in nicardipine- and enalapril-treated SHR (-4.2 plus/minus 0.2% and -4.9 plus/minus 0.2% of control/mm Hg, P < .01, respectively), and the heart rate gain was improved markedly in atenolol- and enalapril-treated SHR (-4.1 plus/minus 0.2 and -4.4 plus/minus 0.2 bpm/mm Hg, P < .01, respectively). In the late-start groups, the renal sympathetic nerve activity gain was improved moderately in nicardipine- and enalapril-treated SHR (-3.8 plus/minus 0.2% and -2.9 plus/minus 0.2% of control/mm Hg, P < .05, respectively). The heart rate gain was improved slightly only in nicardipine-treated SHR (-1.9 plus/minus 0.2 bpm/mm Hg, P < .05). These results demonstrate that an early start of antihypertensive treatment improves baroreceptor reflex function markedly compared with a late start of treatment. This supports the hypothesis that a possible critical phase sensitive to intervention with antihypertensive treatment exists during the development of hypertension and indicates that the early start of antihypertensive treatment would be required in clinical practice. (Hypertension. 1996;27:209-218.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Recent reports indicate that alpha 1-Sodium,Potassium-ATPase from Dahl salt-sensitive (DS) rats contains a glutamine for leucine substitution associated with increased Sodium-Potassium coupling at unchanged maximal velocity. Genetic analyses suggest that alpha-1-Sodium,Potassium-ATPase is a potential hypertension gene. Therefore, we investigated whether renal Sodium+metabolism could constitute a pathophysiological link between the molecular/functional change in Sodium,Potassium-ATPase and hypertension. We simulated the consequences of increased Sodium-Potassium coupling on overall Sodium-bicarbonate reabsorption in a proximal tubular transport model that incorporates apical Sodium-Hydrogen exchanger and basolateral Sodium-bicarbonate cotransporter, Potassium+channel, and Sodium,Potassium-ATPase. As expected, increases in the levels of the former three transport pathways yielded higher Sodium+reabsorption. In contrast, increases in the maximal velocity of the Sodium,Potassium-ATPase with a normal 3:2 (Sodium-Potassium) coupling ratio did not increase Sodium+reabsorption when apical Sodium-Hydrogen exchange activity was limiting overall absorption. However, an increase in the Sodium-Potassium coupling from 3:2 to 3:1, reported for the mutant alpha 1-Sodium,Potassium-ATPase in DS rats, was associated with greater Sodium+reabsorption. This increase is a consequence of lower cytosolic pH and secondary stimulation of the Sodium-Hydrogen exchanger at its allosteric Hydrogen+site. Decreased pH results from activation of Sodium-bicarbonate co-transport by Sodium,Potassium-ATPase-dependent membrane hyperpolarization due to greater charge movement in 3:1 Sodium-Potassium coupling. Thus, an increase in the Sodium-Potassium coupling ratio results in an altered set point for cellular Sodium+metabolism, with higher Sodium reabsorption at unchanged Sodium,Potassium-ATPase levels. The simulations thereby lend support for a unifying explanation for the salt sensitivity of DS rats, which has been proposed to stem from a mutation in the alpha 1-Sodium,Potassium-ATPase. (Hypertension. 1996;27:219-227.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To investigate the potential mechanisms by which indigo carmine produces hypertension, we tested the hypothesis that indigo carmine inhibits endothelium-dependent vasodilation and determined the possible site of the inhibition (endothelium versus smooth muscle). Using isolated rat thoracic aortic rings that were precontracted with phenylephrine, we examined vasodilatory responses to acetylcholine, histamine, and Calcium2+ionophore A23187 (in endothelium-intact rings) and sodium nitroprusside and isoproterenol (in endothelium-denuded rings) in the presence and absence of indigo carmine. In addition, the effects of methylene blue on the acetylcholine- and sodium nitroprusside--induced vasodilation were compared with those of indigo carmine. Indigo carmine (10-6, 10-5, and 10-4mol/L) significantly inhibited receptor- and non-receptor-mediated endothelium-dependent vasorelaxation. Indigo carmine (10-4mol/L) also inhibited endothelium-independent vasorelaxation induced by sodium nitroprusside (an activator of vascular smooth muscle soluble guanylyl cyclase), although to a lesser extent than vasodilation from acetylcholine, histamine, and Calcium2+ionophore A23187. In contrast, indigo carmine (10-4mol/L) had no effect on the vasodilation induced by isoproterenol (an activator of adenylyl cyclase), indicating that indigo carmine selectively inhibits nitric oxide-mediated responses. Methylene blue, a known inhibitor of soluble guanylyl cyclase, inhibited both acetylcholine- and sodium nitroprusside-induced vasorelaxation. The inhibition was also greater in the acetylcholine- than the sodium nitroprusside--induced vasodilation. These results suggest that indigo carmine, like methylene blue, may inhibit endothelium-dependent relaxation by a mechanism that involves two levels. The major action of indigo carmine appears to be at the level of nitric oxide generation and/or release from the endothelial cell. In addition, indigo carmine appears to inhibit vascular smooth muscle guanylyl cyclase. Thus, indigo carmine may elevate blood pressure by interfering with these nitric oxide--mediated vasodilatory mechanisms. (Hypertension. 1996;27:228-234.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID