ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Since glomerular and vascular atrial natriuretic factor (ANF) receptor density may vary inversely with circulating ANF concentration, and the latter may respond to changes in blood pressure, we investigated whether ANF receptors are modified by a pressor agent, angiotensin II. Rats were infused intraperitoneally for 6 days with either a non-pressor (200 ng/kg per min) or pressor dose (800ng/kg per min) of angiotensin II. Blood pressure was higher and plasma renin activity lower in the pressor than in the non-pressor or sham-infused groups. Plasma ANF was elevated only in animals infused with a pressor dose of angiotensin II. Glomerular ANF receptor density was higher in the non-pressor (Bmax= 1308 ± 360fmol/mg protein) and lower in the pressor (Bmax=459 ± 13fmol/mg protein) than in the sham-infused group (Bmax=755 ±303 fmol/mg protein). In vitro, angiotensin ll-precontracted isolated glomeruli from animals infused with a pressor dose of angiotensin II were less sensitive to the relaxant effect of low ANF concentrations (10-12and 10-11mol/l) than those receiving a non-pressor dose of angiotensin II or sham-infused. Vascular ANF receptor density was similar in the control and non-pressor groups (Bmax=64 ±12 and 62 ± 20fmol/mg protein, respectively) and decreased in the pressor group (Bmax=30 ±4 fmol/mg protein). Norepinephrine-precontracted aorta strips from rats receiving a non-pressor dose of angiotensin II were more sensitive to the relaxant effect of ANF. We conclude that glomerular and vascular ANF receptors may be regulated by angiotensin II in the absence of any change in plasma ANF. Once plasma ANF levels are elevated, there is a decrease in the density of both vascular and glomerular ANF receptors.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study investigates the potential utility of a drug concentration-effect modelling approach to predict the long-term response to antihypertensive treatment with enalapril. Concentration-effect relationships were characterized in 13 subjects following a single dose of enalapril (20 mg) and for each individual the derived parameters were used to predict the steady-state blood pressure profile. The predicted responses (before dosing and 4 h after dosing) were in close agreement with the responses observed after 6 weeks. In individual patients, the observed and predicted blood pressure profiles over a 12 h period were compared. In six of the 13 subjects, there were statistically significant (P< 0.05) prediction errors. However, in all but one of these patients the error was < 10%, and for the group as a whole the mean prediction error was small and not statistically significant ( — 0.6 ±.1 mmHg). The kinetic-dynamic parameters derived from observations of the first dose were used to simulate steady-state responses to several alternative doses and dose frequencies. A regimen of 10 mg twice daily increased the ratio of blood pressure at trough-to-peak response to 75 ±5% compared to 33± 16% when 20 mg was given once daily. In addition, a twice-daily regimen reduced the coefficient of variation of the hourly average blood pressure. Thus, concentration-effect parameters derived from the first dose response to enalapril have potential not only for predicting long-term antihypertensive response, but also for optimizing dosage regimens for individual patients.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effects of genetic factors and blood pressure levels on heart and kidney weights were estimated in a set of recombinant inbred (Rl) strains obtained by crossing normotensive rat (BN.Ix) and genetically hypertensive rat (SHR) progenitor strains. Renal or cardiac hypertrophy in several normotensive Rl strains, together with low organ weights in some hypertensive strains, indicate that genetic factors play an important role in heart and kidney weight determination. In Rl strains, there was a slight positive correlation between systolic blood pressure and relative heart weight, while relative kidney weight correlated negatively with blood pressure. Indeed, the analysis of the degree of genetic determination in Rl strains revealed higher values for the relative kidney weight than for the relative heart weight. Blood pressure has a lower degree of genetic determination than both organs. Several polymorphic loci were found to be associated with organ weight determination. Thus, the analysis of organ weights in Rl strains revealed the influence of primary genetic factors rather than secondary blood pressure effects.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Tritiated yohimbine binding was used to estimate platelet membrane α2-adrenoceptor characteristics in normal subjects (n = 12) and patients with essential hypertension (n = 30), primary hyperaldosteronism (n = 10) and phaeochromocytoma (n = 10). There was a 20-fold increase in mean levels of resting norepinephrine and epinephrine in the phaeochromocytoma group. Total binding sites (Bmax) and dissociation constant (Kd) for3H-yohimbine did not differ significantly among the four groups. Following curative surgery for phaeochromocytoma, plasma catecholamine levels were normalized but the Bmaxremained unchanged. Following surgery for primary hyperaldosteronism, levels of plasma norepinephrine rose but Bmaxwas not changed. In all but the phaeochromocytoma patients, Bmaxvalues correlated positively (r = 0.437, n = 48, P < 0.01) with resting plasma norepinephrine. A significant negative correlation was observed between the change in plasma norepinephrine in response to postural change and resting Bmax. Treatment for 2–4 weeks with guanabenz or bethanidine induced a parallel fall in both Bmaxand plasma norepinephrine. Treatment with reserpine was followed by a comparable fall in plasma norepinephrine, but Bmaxvalues were unchanged. The findings support the view that platelet α2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than circulating catecholamine levels, although it is not known which neuronal substance(s) may participate in this regulation.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Using a discriminative classical conditioning paradigm, this study addresses the question of whether vascular responses are more easily acquired or slower to extinguish in mild hypertensives than in normotensive controls. We subjected 18 mild hypertensives, with a resting systolic/diastolic blood pressure of 141/00 mmHg, and 17 normotensive controls similar in age, with resting systolic/diastolic blood pressure 122/80 mmHg, to a discriminative Pavlovian conditioning paradigm with tones of 8 s duration serving as conditioned stimuli (CS) and a mild electric shock as an unconditioned stimulus (UCS). Digital finger pulse volume (FPV) responses were recorded during an acquisition phase, where CS +, but not CS —, was repeatedly paired with the UCS (12 trials), and an extinction phase where shocks were withheld (12 trials). During the acquisition phase, mild hypertensives displayed greater anticipatory vasoconstrictive responses both to CS+ and CS —compared with normotensive controls. In addition, unconditioned FPV responses were enhanced in mild hypertensives. During the extinction phase, mild hypertensives evidenced increased resistance to extinction since conditioned vasoconstriction was more frequently observed in response to CS + than to CS — in mild hypertensives only. Thus, vascular dysregulation in mild hypertensives was evident both for unconditioned and conditioned vasoconstriction. Data are compatible both with a centrally determined increased conditionability in mild hypertensives compared with normotensive and with a decreased threshold for peripheral vascular responsiveness among mild hypertensives.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have studied the effect of parathyroidectomy on the systolic blood pressure, cardiovascular reactivity and the contractile response of isolated aorta to norepinephrine in the genetically hypertensive Lyon rat strain (LH), parathyroidectomized hypertensive Lyon rats (LH-PTX) and parathyroidectomized hypertensive Lyon rats given a Ca-enriched diet to re-establish normocalcemia' (LH-PTX + Ca). Parathyroidectomy significantly lessened (—20%) the development of elevated blood pressure. In the LH-PTX + Ca, the blood pressure was lower than that of LH controls but was higher than that of LH-PTX. At 23 weeks, in vivo responsiveness to norepinephrine and angiotensin II was significantly lower in the LH-PTX and only slightly decreased in the LH-PTX + Ca. In contrast, at the same age, the in vitro contractile response of isolated aortas to norepinephrine was significantly higher in the LH-PTX compared with other groups. Interestingly, without endothelium, this difference disappeared. In conclusion, parathyroidectomy lessened the blood pressure elevation in the Lyon model of hypertensive rats via mechanisms that are partly independent of serum calcium levels

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The reactivity of human veins, biopsied from the forearms of 15 patients with untreated primary hypertension and 14 normotensive subjects, was studied in vitro. Veins of hypertensive patients were less distensible since the slope of their wall tension-circumference relationships was steeper than in normotensive subjects. There was no difference between the groups with regard to their sensitivity (location of the concentration corresponding to 50% of the maximum response) or their normalized maximum contractile force (Fmax/unit radius) in response to potassium or serotonin. However, veins from hypertensive subjects were less sensitive to noradrenaline and the selective α2-adrenoceptor agonist UK14304, and showed a fall in normalized Fmaxwith all α -adrenoceptor agonists. In contrast, in veins from hypertensive subjects, normalized Fmaxwas 3.7 times higher in response to angiotensin II than in veins from normotensive subjects. Despite the reduced responses to exogenous α -adrenoceptor agonists, contractile responses to transmural field stimulation were enhanced in veins from hypertensive subjects. The effect of selective α2-adrenoceptor blockade suggested a decrease in prejunctional autoinhibition, while the effect of desipramine on field stimulation and tritiated noradrenaline efflux suggested a decreased neuronal amine uptake in veins of hypertensive patients. There was no evidence of medial hypertrophy in the veins of hypertensive subjects. We conclude that veins in hypertension are stiffer, have reduced α -adrenoceptor responsiveness, and generate a greater Fmaxin response to angiotensin II and nerve stimulation when compared with veins from normotensive subjects.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID