摘要:

Endothelins are a family of potent vasoconstrictor peptides released by endothelial cells. The production of endothelin-1 (ET-1) can be stimulated by aggregating platelets and angiotensln II. It is inhibited by increases in intracellular concentration of cyclic GMP. ET-1 causes biphasic changes in arterial blood pressure and of peripheral resistance in several vascular beds: an initial transient decrease (due to release of nitric oxide, prostacyclin, or both from the endothelium) followed by a sustained increase (mainly due to direct activation of vascular smooth muscle). The vasoconstriction induced by the peptide is inhibited by increases in cyclic GMP. Few studies, except in pregnant women with preeclampsia or eclampsia, indicate that the circulating levels of the peptide are augmented in hypertension. Likewise, the information available on changes in responsiveness to endothelins in blood vessels from hypertensive animals is controversial. Until the effect of selective antagonists on the production or action of the peptide can be determined in hypertensive patients, caution must be exerted when implying a role for endothelin in the pathophysiology of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The present study investigates morphological renal lesions in sinoaortic-denervated dogs 1 (n=6) and 18 (n=5) months after sinoaortic denervation compared with sham-operated controls (n=8). After 1 month, a marked hyalinization and moderate thickening of the media of arterioles and small interlobular arteries were observed. These changes associated with edema and intimal thickening led to a narrowing of the lumen. In glomeruli, increase of mesangial matrix was focally present in all cases and associated with mesangial proliferation. In four of six cases, some glomeruli appeared retracted, with a large urinary space. A focal area of interstitial fibrosis occurred in just one case. After 18 months, similar but more pronounced vascular lesions were present, with marked hyperplasia of the media. Glomerular changes were characterized by mesangial lesions associated with focal glomerular sclerosis and thickening of Bowman's capsule. Tubulointerstitial lesions were more prominent in this group, with the presence of tubular epithelial changes and casts. Focal interstitial fibrosis, infiltrates, or both were demonstrated in all cases. These morphological lesions were associated with an increase in arterial blood pressure, proteinuria, and natriuresis and a decrease in urinary kallikrein. These results show that chronic sinoaortic denervation in dogs is associated with renal lesions similar to those observed in other well-established experimental and clinical hypertensive states.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Dopamine is a natriuretic hormone that acts by inhibiting tubular Na+JC+-ATPase activity by activation of the dopamine-1 receptor (the thick ascending limb [TAL] of Henle) or by a synergistic effect of dopamine-1 and dopamine-2 receptors (the proximal tubule). The dopamine-1 receptor is coupled to adenylate cyclase. In this article we show that prehypertensive Dahl salt-sensitive (DS) rats have a blunted natriuretic response to dopamine determined during euvolemk conditions compared with Dahl salt-resistant (DR) rats. Furthermore, we have examined the renal tubular effects of dopamine in DS and DR rats. Basal Na+, K+-ATPase activity was similar in DS and DR rats. In proximal tubule, dopamine (10−5M) inhibited Na+, K+-ATPase activity in DR but not in DS rats. The dopamine-2 agonist LY171555 (10−5M) together with dibutyryl cyclic AMP (10−6M) inhibited proximal tubule Na+, K+-ATPase activity in both DS and DR rats. LY171555 alone had no effect In TAL, the dopamine-1 agonist fenoldopam (10−5M) inhibited Na+,K+- ATPase activity in DR but not in DS rats. Dibutyryl cyclic AMP (10−5M) inhibited TAL Na+,K+-ATPase activity in both DS and DR rats. In cell suspensions from the cortex and the medulla, activation of the dopamine-1 receptor significantly increased cyclic AMP content in DR but not in DS rats. The results indicate that DS rats lack the capacity to inhibit tubular Na+,K+-ATPase activity because of a defective dopamine-1 receptor adenylate cyclase coupling. This defect may contribute to the impaired natriuretic capacity in DS rats.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To evaluate the role of the sodium pump in resistance control in vivo, we studied vascular responses to potassium, which produces vasodilation by the activation of vascular Na+,K+-ATPase, in nonnotensive volunteers receiving a high salt diet compared with volume-depleted subjects receiving diuretic treatment Forearm blood flow was measured by strain-gauge plethysmography during small increments in local concentrations of potassium with intrabrachial arterial infusions of KCl. Infusions of 0.12 and 0.24 mEq/min KCl increased forearm blood flow and decreased forearm vascular resistance in a dosedependent fashion. But the simultaneous intrabrachial arterial infusion of 2 μg/min ouabain, a Na+,K+-ATPase inhibitor, could blunt the decremental response of vascular resistance to 0.12 mEq/min KCl. The decrements of vascular resistance with KCl infusions divided by the initial resistance were significantly less with ouabain compared with those without ouabain (43±4% versus 57±3%,p<0.01). This suggests that potassium produces vasodilation by the activation of vascular Na+,K+-ATPase activity. Similarly, salt loading (180 mEq NaCl for 7 days) after treatment with diuretics could attenuate percent decrements of resistance with KCl infusions (39±3% versus 53±2%,p<0.01), whereas vascular resistance responses to sodium nitroprusside, a nonspecific vasodilator, and to verapamil, a calcium antagonist, did not change with salt loading after volume depletion. Therefore, salt loading could attenuate forearm vascular response to potassium specifically, as did the administration of ouabain. Evidence supports the hypothesis that volume expansion with salt loading increases endogenous ouabainlike Na+,K+-ATPase inhibitor concentration, which plays a role in not only the control of extracellular fluid but also the regulation of vascular tone during salt loading.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Diets high in sucrose or fructose have been shown by others to induce a modest elevation of blood pressure in rats. The present experiments were conducted to determine whether the sucrose-induced increase of blood pressure is dependent on the intake of sodium chloride. Four groups of Sprague-Dawley rats were studied: 1) a group maintained on a low salt diet and distilled water (0.45% sodium chloride, no added sucrose), 2) a low salt-high sucrose group (0.45% sodium chloride diet and 7% sucrose in distilled water), 3) a high salt group (4% sodium chloride diet and distilled water), and 4) a high salt-high sucrose group on a diet adjusted dairy to maintain the same high intakes of sodium chloride and sucrose as those of groups 2 and 3. Systolic blood pressures were measured by tail-cuff plethysmography during weeks 1-3 of treatment, and direct mean arterial blood pressures were recorded in conscious animals during week 4. Animals on the high salt diet gained weight more slowly than those on the low salt intake. On the low sodium chloride intake, blood pressures were not affected by high dietary sucrose (group 1 versus 2). In contrast, on the high sodium chloride intake, blood pressures were 10-14 mm Hg higher in sucrosedrinking animals than in water-drinking animals (group 3 versus 4). The increments in blood pressures of the high sodium chloride-high sucrose group were not accompanied by greater increments in body weight compared with the animals on the high sodium chloride intake alone. Sucrose-fed animals exhibited an increase in basal plasma norepinephrine concentrations and increased responsiveness of both norepinephrine and epinephrine to stress (mild electrical foot shock), regardless of the sodium chloride intake. Thus, in the Sprague-Dawley rat, sucrose elevates blood pressure only when adequate salt is present in the diet We hypothesize that a high sucrose intake may activate the sympathetic nervous system but that this activation is effective in elevating blood pressure only when there is a concomitant high intake of sodium chloride.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The effects of long-term treatment with captopril and conventional therapy on albuminuria and metabolic parameters were compared in 74 hypertensive type II diabetics with normal serum creatinine. Patients were treated double-blind with either captopril monotherapy or combined with hydrochlorothiazide or therapy with metoprolol, hydrochlorothiazide, or both for 36 months. The treatment was titrated to achieve goal diastolic blood pressure of ≤85 mm Hg. The reductions in blood pressures during treatment were similar in patients with (n=21) and without (n=53) microalbuminuria treated with either captopril or conventional therapy. No significant changes in albuminuria occurred in normoalbuminuric patients with either therapy. Although albuminuria fell in nearly all patients with microalbuminuria treated with captopril, it rose in eight of 12 patients on conventional therapy, with macroalbuminuria developing in two of them. Renal function was preserved by both types of treatment in both patient groups. Long-term treatment with either conventional therapy or captopril did not alter metabolic variables. We conclude that captopril alone or in combination decreases albuminuria and prevents the development of macroalbuminuria in hypertensive type II diabetics with persistent microalbuminuria. The renoprotective effect of this agent, however, remains to be demonstrated with longer term data on renal function. Aggressive antihypertensive treatment with either captopril or conventional therapy appears to be effective in preventing the onset of microalbuminuria in most normoalbuminuric patients. In contrast, with previous short-term studies, the use of converting enzyme inhibitors or conventional therapy did not cause adverse metabolic effects.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Calcium entry blockers, particularly diltiazem, have been shown to lower not only systemic blood pressure but also improve proteinuria in non-insulin-dependent diabetic patients. The presence of proteinuria is attributed to the loss of glomerular heparan sulfate, which confers a negative charge on the basement membrane. In the present study, we evaluated the efficacy of diltiazem in lowering blood pressure and proteinuria in diabetic rats and also examined the possibility that diltiazem prevents proteinuria through glomerular preservation of heparan sulfate. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg). One group of diabetic rats was treated with diltiazem (25 mg/L) in drinking water for 20 weeks. Another group of diabetic rats and a group of nondiabetic rats were given tap water only. Systolic blood pressure was measured at 4, 8,12, and 20 weeks. Urinary excretion of albumin was done at 4, 8,12, 16, and 20 weeks. At the end of 20 weeks, all rats were killed, kidneys were removed, and glomeruli were isolated. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of [35S] sulfate. Diltiazem lowered blood pressure significantly in diabetic rats at 8,12, and 20 weeks. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from normal rats. Characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. Diltiazem therapy returned not only glomerular synthesis but also various fractions of heparan sulfate to normal. Urinary albumin excretion was significantly higher in diabetic than in normal rats; diltiazem therapy significantly lowered albuminuria in diabetic rats. The data suggest that diltiazem therapy prevents albuminuria through preservation of glomerular heparan sulfate in diabetic rats.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To evaluate the atrial natriuretic peptide response to angiotensin II (Ang II) infusion in non-modulating hypertension, we studied 31 men with essential hypertension. These patients were subdivided into groups of low renin patients (n=8), non-modulators (n=11), and modulators (n=12) according to their renin profile and ability to modulate renin and aldosterone responses to a graded infusion of Ang II (1.0 and 3.0 ng/kg per minute) on a low Na+intake (10 mmol Na+per day). During basal conditions, plasma atrial natriuretic peptide was higher (p<0.05) in low renin patients (1634±2.67 fmol/mL) than in both modulators (10.59±4.29 fmol/mL) and non-modulators (9.85±2.64 fmol/mL). During Ang II infusion, plasma atrial natriuretic peptide significantly increased in both low renin (27.67±2.61 fmol/mL at 60 minutes,p<0.01) and modulating (20.36±3.07 fmol/mL at 60 minutes,p<0.05) patients, whereas it did not change in non-modulators (13.94±439 fmol/mL, NS). After 5 days on a high sodium intake (200 mmol Na+per day), plasma atrial natriuretic peptide rose in modulating (20.61±2.3l fmol/mL,p<0.01 versus low sodium intake), non-modulating (20.11±6.48 fmol/mL,p<0.01 versus low sodium intake), and low renin (26.13±3.81 fmol/mL,p<0.001 versus low sodium intake) hypertensive patients. When the Ang II infusion was repeated with a high sodium intake, plasma atrial natriuretic peptide increased again in low renin and modulating patients, whereas it did not change in non-modulators. Therefore, these data indicate that an impaired atrial natriuretic peptide responsiveness to Ang II that is not dependent on Na+intake may represent another characteristic of the non-modulating phenotype.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The effects of four different antihypertensive drugs (the Ca2+-channel blocker felodipine, the β-blocker metoprolol, the angiotensin converting enzyme inhibitor ramipril, and the α-blocking agent doxazosin) on microalbuminuria and renal hemodynamics were evaluated in a double-blind, crossover study in 17 patients (10 women, seven men, aged 39 ±14 years) with mild-to-moderate essential arterial hypertension and microalbuminuria. Patients were studied after a 2-week placebo phase preceded by 2 weeks off all medication and after 12 weeks of treatment with each drug. Between each drug treatment, there was another 14-day placebo washout period. At the end of the study, we performed two additional 2-week placebo periods. After each placebo and treatment period, we measured albumin excretion during a 3-day collecting period. Renal hemodynamics were assessed by clearance techniques (inulin andp-aminohippurate clearance) at the end of the first and last placebo periods and after each treatment period. All drugs reduced mean arterial pressure and microalbuminuria to a similar and statistically significant (p<0.05) extent (mean arterial pressure: placebo phase, 116±5 mm Hg; felodipine, 101±4 mm Hg; metoprolol, 101±5 mm Hg; ramipril, 101±4 mm Hg; doxazosin, 102±5 mm Hg; urinary albumin excretion: placebo phase, 46±50 mg/day; felodipine, 18±23 mg/day; metoprolol, 14±12 mg/day, ramipril, 16±16 mg/day, doxazosin, 14±14 mg/day). Mean arterial pressure levels and urinary albumin excretion returned to baseline after the last placebo period (110±6 mm Hg and 40±46 mg/day, respectively). Glomerular filtration rate and renal plasma flow were not significantly changed by any drug and were normal in all patients. Renal vascular resistance and filtration fraction were lowest during angiotensin converting enzyme inhibition, but these differences did not reach statistical significance. In conclusion, all types of antihypertensive drugs under investigation reduced microalbuminuria in patients with mild-tomoderate arterial hypertension and without an elevation in filtration fraction. In the case of essential arterial hypertension, reduction of blood pressure seems to be an important factor for treatment of albuminuria.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID