摘要:

SUMMARY The renal effects of two structurally dissimilar inhibitors of prostaglandin synthesis (Meclofenamate and RO-20-5720) were studied in conscious, chronically instrumented dogs during mild volume expansion and during a constant infusion of furosemide. When either inhibitor was administered following volume expansion, urinary excretion of PGE2and urine flow rate were reduced by more than 50%. In contrast, renal plasma flow fell by less than 10% while glomerular filtration rate, sodium excretion, and plasma renin activity (PRA) were unchanged. In separate studies, infusion of furosemide increased renal plasma flow, urine flow rate, sodium excretion, PRA, and urinary excretion of PGE, while glomerular filtration rate decreased. Administration of inhibitors of prostaglandin synthesis during constant infusion of furosemide reduced the urinary excretion of PGE, to control levels, as renal plasma flow and glomerular filtration rate fell below control level. Despite these hemodynamlc alterations, the furosemide-induced diuresis and increase in PRA were only partly attenuated by prostaglandin inhibition. It is concluded that in conscious dogs, intrarenal prostaglandins modulate urine flow rate during mild volume expansion and play a major role in mediating the renal hemodynamic effects of furosemide.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Experiments were conducted on two-kidney, one clip renal vascular hypertensive rats to assess the ability of the kidney contralateral to renal vascular stenosis to autoregulate renal blood flow (RBF), glomerular filtration rate (GFR), and hydrostatic pressures in cortical structures during conditions of acutely reduced renal arterial blood pressure (BP). When observed at their respective, spontaneous BPs, RBF and GFR were not different in the contralateral kidneys of the hypertensive rats (n = 11) compared to normal animals (n = 7). However, the contralateral kidneys exhibited a significantly higher renal vascular resistance (RVR), 28.9 ± 2.8 mm Hg min/ml than the control animals, 23.1 ± 1.5 mm Hg min/ml. At spontaneous BP (169 ± 5 mm Hg), urine flow, absolute and fractional sodium excretion, and absolute and fractional potassium excretion were all significantly greater in the contralateral kidneys of hypertensive rats than in kidneys of normal rats. Hydrostatic pressures in cortical structures were similar in the two groups. When BP was reduced acutely, the kidney comralateral to the renal artery stenosis achieved only small decreases in RVR that failed to allow RBF, GFR, or cortical pressures to be maintained. In contrast, normal rats efficiently autoregulated RBF and GFR. In addition, hydrostatic pressures in proximal tubules, distal tubules, and first order peritubular capillaries were maintained during reductions in BP to as low as 100 mm Hg. Urine flow and electrolyte excretion decreased to a greater extent in the hypertensive kidneys, such that at comparable BP these indices of excretory function were not different in the two groups. These observations indicate that the capacity of the contralateral kidney to maintain hemodynamic and glomerular function at reduced BP is compromised severely and suggest the possibility that the impaired autoregulatory capability may contribute to the maintenance of hypertension observed in this model.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY This study investigated whether the riboflavin analogs, 7,8-dimetfayl-10-formylmethyl isoalloxazine (FMI) and 7,8-dimethyl-10-(2'-hydroxyethyl) isoalloxazine (HEI), are effective antihypertensive agents in mineralocorticoid-induced or deoxycorticosterone acetate (DOCA)-salt hypertension. These studies are based on our previous observation that aldosterone enhances the biosynthesis of renal flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) from riboflavin, and that FMI and HEI competitively inhibit conversion of riboflavin to FMN and reabsorption of Na+in the kidney of adrenalectomized rats. When 1.6 mg of FMI or HEI were administered simultaneously with 3.0 mg of DOCA, the tail systolic blood pressure (SBP) of unanesthetized rats rose only to 136 ± 5 mm Hg (standard error of the mean, SEM) compared to 163 ± 5 mm Hg during DOCA therapy alone (p< 0.0005). This hypotensive effect of FMI or HEI was noted after the fourth week of treatment and persisted through the ninth week. The rats tolerated the medication well and had no signs of riboflavin deficiency.DOCA administration alone resulted in a 24% increase in iliopsoas muscle Na+concentration (p< 0.0005), and a 0.8% increase in the water content of the muscle (p< 0.025), suggesting a positive Na+balance. Administration of FMI or HEI blunted the ability of DOCA to increase muscle Na+concentration (p< 0.025), water content (p< 0.01). HEI treatment of the Kyoto strain of spontaneously hypertensive rats (SHR) did not lower their mean SBP. Thus it appears that the hypotensive actions of FMI or HEI are closely associated with their ability to modify the effects of mineralocorticoids on Na+balance.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Tonin has been purified from rat submaxillary glands. The purification procedure included affinity chromatography on Sepharose 4B coupled to antitonin followed by DEAE chromatography and gel filtration on Sephadex G-100. Homogeneity of the purified enzyme was confirmed by Sephadex G-100 gel filtration, disc electrophoresis, and isoelectric focusing on polyacrylamide gel, immunodiffusion, and immunoelectrophoresis. The tonin was purified 11.5-fold, with 35% recovery. The purified tonin has full enzymatic or immunological activity.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY To determine the effect of diabetes mellitus on the renin-aldosterone system, independent of age, nephropathy, or hypertension, 16 nonnotensive diabetics with long-term disease (mean duration, 15 years) and no (14) or minimal (2) proteinuria, were compared to nine age-matched, normotensive controls. Plasma renin activity (PRA) measured supine and after 4 hours of quiet ambulation, both on an ad libitum diet and on Day 4 of a 10 mEq low sodium diet, was always lower in the diabetics (31%-56% of control values). After the combined stimulus of sodium depletion and ambulation, PRA was 2.2 ± 0.4 in the diabetics compared to 3.4 ± 0.2 ng/ml/hr in controls (p< 0.025).On the low sodium diet, PRA and the postural response of PRA correlated directly with the degree of autonomic dysfunction as quantitated by the velocity of esophageal peristalsis (r= 0.60,p< 0.05;r= 0.75,p< 0.005 respectively), suggesting that autonomic neuropathy was an important factor contributing to low PRA in these patients. No other parameters correlated with PRA. Plasma renin substrate (PRS) tended to be lower in diabetics (1053 ± 95 vs 1358 ± 132 ng AI/ml;p< 0.07) but not sufficiently so to account for the substantial difference in PRA. Furthermore, PRS did not correlate with PRA. Fasting blood sugar, while higher in diabetics (209 vs 96 rag/dl), and creatlnlne clearance, which was lower (112 ± 13 vs 78 ± 4 ml/min;p< 0.01), also did not correlate with PRA. Other factors, including serum creatlnlne, serum potassium, urinary aldosterone, blood pressure, and body weight, and the responses of these parameters to sodium depletion, were similar in diabetics and controls. These data Implicate visceral neuropathy as a major factor in the hyporeninemia of these diabetics.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY The goal of this study was to compare adrenergic neurotransmlssion in isolated vascular smooth muscle from spontaneously hypertensive (SHR) and normotensive rats. Tail arteries, excised from adult SHR and normotensive rats, were cut helically into strips that were mounted in organ chambers between two platinum wire electrodes; isometric contractions were recorded. Vascular responsiveness was determined before and after acute denerration with 6-hydroxydopamine or before and after treatment with phentolamine. Release or displacement of endogenous norepinepbrine was obtained with electrical stimulation, tyramine, and potassium. The sensitivity to exogenous noreplnephrine of innervated vessels was similar for SHR and normotensive rats. Denerration produced a significant shift to tbe left in the concentration-response curve to noreplnephrine only in SHR vessels. Contractile responses to electrical stimulation, tyramine, and potassium were similar in both groups before denervation. Contractile responses to potassium-free solution were greater in SHR than in normotensive vessels. Following denerration, the SHR and normotensive vessels responded similarly to these latter interventions. Blockade of alpha-adrenoceptors with phentolamine reduced contractile responses to all agents in innervated and denerrated vessels. Cocaine caused a slowing of the relaxation following contraction induced by electrical stimulation in both SHR and normotensive vessels. The relaxation of SHR vessels was less affected by cocaine than in normotensive vessels. The tissue content of norepinephrine was similar in SHR and normotensive arterial strips. In arterial strips from SHR the uptake of 'H-norepinephrine was significantly larger than in those from normotensive rats. The results suggest that the reactivity of innervated blood vessels to $$ norepinephrine is similar in SHR and normotensive rats. Important differences in sensitivity to norepinephrine in hypertensive vessels are unmasked when tbe relationship between the vascular smooth muscle cell and the adrenergic nerve terminal is altered. Apparently, the adrenergic nerve terminals in hypertensive blood vessels can modulate the junctional concentration of norepinephrine so that the contractile response to this agent is similar to that in normotensive blood vessels.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Whole-body venous capacity was examined in conscious 4-roonth-old male spontaneously hypertensive rats (SHR) and Wlstar-Kyoto normotensive (WKY) rats by determining mean circulatory Ailing pressure (MCFP) and blood volume. The MCFP was determined in conscious animals after briefly arresting the circulation by inflating an indwelling balloon in the right atrium. Blood volume was determined by dilution of "M-albumin and "Cr-red cells. Although blood volume was not significantly different between SHR (60.9 ± 0.7 ml/kg, SE) and WKY (59.6 ± 0.8 ml/kg), MCFP was slightly, but significantly elevated in the SHR (9.5 ± 0.3 vs 8.5 ± 0.2 mm Hg, mean ± SE,p< 0.05). Increased MCFP with normal blood volume suggests decreased venous capacity in the SHR. In addition, effective total tissue compliance (ETTC) was measured in conscious 5-month-old female SHR and WKY. A decrease in tissue fluid volume was induced by i.v. infusion of hyperoncotic albumin solution. Changes in interstitial fluid pressure were monitored continuously with implanted tissue capsules. Changes in tissue fluid volume were estimated from changes in plasma volume and urine volume. In SHR 3 hours postinfusion, tissue fluid volume decreased by 38.7 ± 2.7 ml/kg and interstitial fluid pressure decreased from &#151;1.4 ± 0.3 to &#151;6.6 ± 1.5 ram Hg. In WKY, tissue fluid volume decreased by 32.5 ± 2.7 ml/kg and interstitial fluid pressure decreased from −1.4 ± 0.4 to −3.9 ± 0.5 mm Hg. The linear regression line for A Interstitial fluid pressure and A fluid volume was estimated for each rat and the inverse of this slope represented ETTC, which averaged 7.4 ± 1.0 and 9.6 ± 2.1 ml/kg/mm Hg (p > 0.3) in SHR and WKY respectively. Thus, there were no significant differences in interstitial fluid pressure or ETTC between female SHR and WKY. The results of this study confirm a decreased venous capacity in male SHR with established hypertension and provide new information indicating no measurable abnormalities in interstitial fluid pressure or effective total tissue compliance in adult female SHR as compared with WKY.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY The decline in blood pressure (BP) in essential hypertensives following hospitalization may result from: 1) regression toward the mean; 2) reduction of anxiety as patients habituate to a new enrironment; 3) the placebo effect of medication; and 4) an independent effect of hospitalization itself. A randomized crossover study of 12 essential hypertensives demonstrated a fall in supine blood pressure from 165.0/97.9 ± 2.3/1.1 mm Hg to 154.3/89.6 ± 2.7/1.1 mm Hg (p< 0.005) due to hospitalization. A similar reduction in BP from 164.9/99.5 ± 8.4/4.1 mm Hg to 151.9/93.4 ± 4.5/1.9 mm Hg (p< 0.005) resulted from regression toward the mean and habituatlon during the study period. Urinary catecholamines fell from 68.7 ± 5.0 to 55.1 ± 4.3 Mg/g creatinine/24 hours (p< 0.05) due to hospitalization and from 56.1 ± 5.4 to 49.7 ± 43 fig/g creatinine/24 hours (p< 0.05) with time. Although placebo therapy tended to reduce BP, it failed to do so significantly. When expressed as a percentage of the individual's overall mean, urinary catecholamine excretion fell from 110.5% ± 3.7% to 89.5% ± 3.7% (p< 0.001) during hospitalization and from 105.8% ± 3.9% to 94.2% ± 3.9% (p< 0.05) during the outpatient period. Blood pressure and sympathetic activity rapidly returned to prehospitalization values on discharge. These factors may confound the analysis of drug effects on BP and sympathetic activity in essential hypertensives following admission to hospital.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY The mean arterial pressure (MAP) of nine sinoaortic denervated (SAD) and eight control rats housed in standard-sized metabolic cages was determined continuously via aortic cannuiae and computerized data collection over 24 hours. These continuous measurements were compared with direct, mean aortic pressure measurements and indirect, tail-cuff systolic pressure determinations made while these rats were resting in a Luclte restralner. Denerrated rats were studied 1 month after debuffering. Both types of measurements made during restraint indicated that the SAD rats were hypertensive; the MAP averaged 145 ± 3.4 mm Hg (mean ± SEM) in SAD rats compared with 119 ± 2.8 mm Hg in the control group (p< 0.001), and the tailcuff pressure in SAD rats was 156 ± 5.4 vs 121 ± 2.7 mm Hg in control rats (p< 0.001). In contrast, continuous monitoring showed that the SAD rats were normotensive; the MAP averaged 119 ± 4.7 mm Hg in the SAD group and 119 ± 3.1 mm Hg in the control group. Denervation increased pressure lability; the average 24-hour standard deviation of MAP was 19.0 ± 1.2 mm Hg in SAD rats vs 8.0 ± 0.7 mm Hg in control rats (p< 0.001). Apparently, arterial pressure is elevated during restraint in SAD rats because buffering by the baroreceptor reflex is absent, and pressure measurements made under these conditions give a false indication of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY We studied the dynamic responses of inactive renln and the form of renin released by the kidney in the hypertensive patients. Significant increase of active renin concentration (p< 0.01) and decrease of the percentage of inactive renin concentration (p< 0.01) after sodium depletion was observed in 15 essential hypertensive subjects with normal plasma renin activity. In eight of 15 patients, significant increase of inactive renin concentration [p< 0.01) was observed after sodium depletion. In the remaining seven patients, no significant change of inactive renin concentration was demonstrated. A small increase of active and inactive renin concentration was observed following sodium depletion in six essential hypertensive subjects with low plasma renin activity (PRA). In the unilateral renal hypertension after upright tilting, active renin concentration in the renal vein of the affected kidney was significantly (p< 0.02) higher than that in the renal vein of the nonaffected kidney and the inferior vena cava. Inactive renin concentration in the renal vein of the affected kidney was significantly (p< 0.02) lower than that in the renal vein of the nonaffected kidney and the inferior vena car a. In four of five cases, the inactive renin concentration in the femoral artery was less than that in the inferior vena cava. Therefore, we might conclude that only active renin was released from the affected kidney, and active renin became inactive by unknown mechanisms; the ischeraic kidney might also activate inactive renin.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID