摘要:

SUMMARY The subcellular distribution and nature of rat renal renin has been Investigated by means of analytical subcellular fractionation and gel filtration on Sephadex G-100. During differential centrifugation, renin activity was recovered mainly in soluble and heary mltochondrial fractions. On sucrose gradient centrifugation in either a conventional or in a B XIV zonal rotor, renin activity equilibrated at 1.54 M sucrose and was partially resolved from marker enzymes for mitochondria (succinate debydrogenase), lysosomes (acid phosphatase), plasma membranes (alkaline phosphatase), and peroxisomes (catalase). On gel filtration of the soluble or extracts of the renin-granular fractions on Sepbadex G-100, renin activity eluted as a single peak with an apparent molecular weight (MW) of 42,000; no change In activity was found when these fractions were acidified to pH 3.0. When kidney homogenates were prepared in the presence of the proteolytic inhibitor N- ethylmaleimide (NEM, 10 mM), whereas the renin from the granular fractions displayed a MW of 44,000, that from the soluble fraction was apparently higher (69,000). Addition of NEM (10 mM) to the soluble fraction previously shown to contain only the low MW form of renin also resulted in an apparently high MW form of renin. These results indicate that rat renal renin is associated with a mechanically fragile, distinct type of subcellular organelle. Renin within this structure is of the low MW form and is not acid activatable. The soluble fraction, however, contains a factors) that, in the presence of NEM, combines with the low MW renin to form a complex of apparently high MW.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY We compared vascular and hormonal responses to teprotide (SQ 20,881) and captopril (SQ 14,225) in patients with normal renin essential hypertension given a 10 mEq sodium diet. In 10 patients receiving SQ 20,881, significant changes occurred in diastollc blood pressure (DBP, −1 3 ± 2.5 mm Hg), angiotensin II (-7.1 ± 2.1 pg/ml), and plasma renin activity (PRA, +6.6 ± 1.9 ng/ml/hr) (p< 0.01 in all cases). Twenty-one patients receiving SQ 14,225 had significant changes in mean DBP (-18 ± 1.5 mm Hg), angiotensin II (-6.6 ± 1.5 pg/ml), and PRA (+7.8 ± 2.4 ng/ml/hr) (all p values < 0.01). In spite of a significantly greater hypotensive response (p< 0.02), patients receiving SQ 14,225 showed increments in PRA and decrements in angiotensin II that did not differ significantly from those seen after SQ 20,881. Moreover, there was a significant change in plasma kinins in patients receiving SQ 20,881 (+2.0 ± 0.9 ng/ml.p< 0.01) but no change in kinins in patients receiving SQ 14,225 (0.0 ± 0.1, ns). We conclude that there are important differences in the mechanism mediating the hypotensire response to SQ 20,881 and SQ 14,225 in normal renin essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY Structural changes in resistance vessels have been demonstrated in humans and animals with established hypertension, and recent animal studies suggest they may be present in the early as well as established stage of hypertension. To determine if there are structural vascular changes In humans with borderline hypertension, we examined the vasodilator capacity of forearm resistance vessels In 11 young borderline hypertensive men (25 ± 1 yrs; mean ± SE), and 14 normotensive men (25 ± 1 yrs). Vasodilator capacity was examined by measuring minimal vascular resistance during peak reactive hyperemia after release of 10 minutes of arterial occlusion. Resting forearm vascular resistance was not significantly different in borderline hypertensive (25.9 ± 1. 8 units) and normotensive (21.6 ± 2.3 units) subjects. However, minimal forearm vascular resistance after release of 10 minutes of arterial occlusion was 40% higher (p< 0.05) in borderline hypertensive (2.1 ± 0.2 units) than in normotensive (1.5 ± 0.1 units) subjects. Increasing the metabolic vasodilator stimulus by performing intermittent handgrip exercise during 10 minutes of arterial occlusion did not augment peak vasodilation; this suggests that 10 minutes of arterial occlusion produced maximal vasodilation. Vascular resistance at peak vasodilation was not increased by lower body negative pressure, which suggests that neurogenic vasoconstriction did not limit peak reactive hyperemia. This study demonstrates that forearm vasodilator capacity is limited in young men with borderline hypertension. This finding suggests that there may be structural changes in forearm resistance vessels in borderline hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY Adrenal function was assessed in control rats and in rats treated for 2 and 4 weeks with 17amethylandrosteriediol (MAD; 17a-methyl-5-androstene-30,170-diol), a synthetic androgen known.to produce hypertensive cardiovascular disease. In both groups and at both time periods, a circadian rhythm of blood corticosteroid concentrations was observed. The high point for serum corticosterone (B), 18-hydroxy-lldeoxycordcosterone (18-hydroxy-DOC), and 11-deoxycorticosterone (DOC) concentrations occurred at the beginning of the dark period (1800 hours), and the low point occurred at the onset of the light period (0600 hours). Serum concentrations of DOC were always found to be higher in MAD-treated rats as compared with controls. The serum concentrations of B and 18-hydroxy-DOC were lower than control values at 1800 hours but higher than control concentrations at 0600 hours. The in vitro 11/3- and 18-hydroxylation of DOC was markedly reduced with MAD treatment. In contrast, cholesterol side-chain cleavage activity was higher in animals treated with MAD. These in vitro findings correlated with spectral studies that showed a decreased binding of DOC to cytochrome P45O1Uand increased binding of cholesterol to cytochrome P450$x. These studies suggest that MAD treatment selectively decreases 11/9- and 18-hydroxylatlon in adrenal mitochondria, and this results in an increased serum concentration of DOC, a hypertensinogenic steroid. This effect of MAD on peripheral serum DOC concentration is most readily observed in quiescent animals at the high point of the circadian rhythm.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY The acute responsiveness of plasma catecbolamine, renln (PRA), and aldosterone levels to exogenous norepinephrine was studied under placebo conditions and following renin-angiotensin activation by diuretic pretreatment in 25 normal subjects and 34 patients with borderllne-to-moderate essential hypertension. Norepinephrine infusion caused increases in plasma norepinephrine (PNE) that correlated with the infused norepinephrine dose (p< 0.001); this relationship was similar in normal and hypertensive subjects and unaltered by diuretic therapy. Plasma eplnephrine and dopamine levels were unchanged during norepinephrine infusion. Norepinephrine infusion at pressor doses stimulated PRA (p< 0.01). The PRA responses correlated with the dose of infused norepinephrine [p< 0.0025), and norepinephrlne-stimolated PRA correlated with basal PRA (p< 0.001). These norepinephrine-PRA relationships were unaltered by diuretic treatment and similar in normal and hypertensive subjects. In both groups, norepinephrine also caused a similar Increase in plasma aldosterone (p< 0.05) under placebo conditions, but not following diuretic therapy. These findings demonstrate that an acute increase in the blood levels of the adrenergic neurotransmittor, norepinephrine, causes mild but distinct stimulation of plasma renin and aldosterone levels. Renin release in response to exogenous norepinephrine is not enhanced following renin-angiotensin activation by diuretic pretreatment. The responsiveness of the renin-angiotensin-aldosterone system to an acute norepinephrine input seems to be intact in essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY We have tested the steady-state predictions of the hypothesis that coarctation hypertension, if renin-mediated via total-renal underperfusion, will be characterized by a persistently abnormal renin/bodyfluid-volume relationship. In six inbred Labrador dogs with neonatally-induced thoracic aortic coarctation and in seven littermate controls, serial measurements of forelimb BP, plasma renin activity (PRA), extracellular (ECV), and plasma (PV) volumes ("Na and '"RISA spaces), and renal function (clearances of inulin and PAH) were performed during varied steady-state sodium intake over 1-12 months post-aortic-banding (PAB). In coarcted dogs, significant forelimb hypertension by indirect technique [p< 0.001) was confirmed by aorticarch pressures at 1 year PAB (182 ± 8/111 ± 8 mm Hg vs 131 4/78 l,p< 0.001/ < 0.01). Significant increases in ECV (386 ± 4 cc/kg in coarcted, n = 80, vs 371 3cc/kg in controls, n 89,p< 0.01), in PV (49 ± 1 cc/kg, n = 76, vs 47 n = 87, In controls,p< 0.025), and calculated blood volume (p< 0.025) in coarcted dogs averaged 4.1%, 4.1%, and 5.1% over littermate controls and were of similar magnitude during normal, low, and high sodium intake. Since PRA in coarcted animals was comparable to control values at each sodium intake (and thus in excess with reference to volume status), the renin/volume curve was displaced upward relative to that of normotensive controls. The maintenance of normal effective renal plasma flow and glomerular filtration rate in coarcted dogs over the first year PAB also fulfills the steady-state predictions for renin-mediated hypertension and suggests that the renal circulation is a major regulated variable in renin-angiotensin-volume homeostasls. We conclude that, during the first year PAB, neonatally-induced coarctation hypertension is characterized by an abnormal renin/volume relationship demonstrable during varied sodium intake and despite an apparently "normal" PRA. While available evidence supports the potential hypertensive impact of this quantitatively small abnormality, its renln-dependence remains to be documented.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY In a double-blind (DB), multicenter, clinical trial, 355 patients with mild-to-moderate essential hypertension, characterized by a diastoiic blood pressure (DBP) of 95-115 mm Hg, received either timoiol (T) 10-30 mg twice-a-day, or placebo (P). After 12 weeks of treatment, the mean supine BP for the T group was 145/94 mm Hg (baseline [BL] = 154/103), and for the P group, 155/102 (BL = 156/103). Fifty-seven percent (74/129) of the patients receiving T and 13% (15/114) of the patients receiving P had a reduction in supine DBP (SDBP) to 90 mm Hg or less or had a reduction greater than 10 mm Hg but not to 90 mm Hg. The reduction in SDBP for the T group was significantly greater than the reduction for the P group. After Week 12, patients responding to T continued to receive T (T/T group), while patients receiving P who did not respond were then treated with T (P/T group). Results obtained after 24 weeks of timoiol treatment for the T/T group and after 12 weeks of timoiol treatment for the P/T group were similar to those observed for the T group at 12 weeks. During the 12-week DB study, the incidence of adverse experiences was not significantly different between the T and P groups. Safety evaluations, including complete ophthalmologic exams, have not revealed any toxic effects for T. Withdrawal of timoiol for 2 weeks after 24 weeks of treatment for the T/T group and after 12 weeks of treatment for the P/T group was not associated with any rebound phenomena.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY It has been suggested that in two-kidney, one clip hypertension, the undamped kidney (UK) actively contributes to hypertension by reducing its excretory ability in response to increased levels of Circulating angiotensin II. By exteriorizing the ureter to the dog's flank several weeks beforehand, we measured renal function directly from the UK of six chrogic renal hypertensive (> 3 weeks) and six normal dogs (ND). Mean blood pressure (indwelling catheter) and renal function were measured in the trained dogs for two 20- minute periods before and during a 40-rainute intravenous infusion of SQ 20,881, at a dose (300 Mg/kg + 3 Mg/kg/min) that caused no changes in blood pressure (BP). In dogs with chronic renal hypertension [121 mm Hg ± 2 SE] and mild elevation of plasma renin activity (2.0 ± 0.4 vs 0.4 ± 0.1 ng/ml/hr in ND), infusion of SQ 20,881 caused marked increases in sodium excretion (UNaV), glomerular filtration rate, and effective renal plasma flow. Moreover, the changes in UNaV and effective renal plasma flow were highly correlated (r= 0.77,p< 0.001). In normotensive dogs (99 ± 2 mm Hg) SQ 20,881 caused a 30% ± 5% rise in UNaV, a modest increase in glomerular filtration rate (4% ± 2%) and no change in effective renal plasma floVr. Infusion of a mild pressor dose of angiotensin II (4 ng/kg/min) produced decreases in sodium excretion, effective renal plasma flow, and glomerular filtration rate in the normotensive dogs. In the hypertensive animals, the same infusion rate of angiotensin II caused significant natriuresis without changes in effective renal plasma flow and glomerular filtration rate. These results suggest that the mild increases in plasma renin activity associated with the chronic phaseof two-kidney, one clip hypertension contribute in modifying the renal function of the untouched kidney.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY Prostaglandins (PG) E, and I, are potent vasodepressor agents and their endogenous release may contribute to the regulation of blood pressure (BP). We Investigated whether a decreased response to or a decreased capacity of tbe rasculature to synthesize rasodepressor PGs could contribute to the increased vascular resistance characteristic of hypertension. The change in mean arterial blood pressure (MAP) to Intraaortic (i.a.) injection of PGE, and PGI, at 0.01, 0.1,1.0, and 10.0 and of sodium nitropnisside (NaNP) at0.1, 1.0 and 10.0 nmoles/100 g body weight (gbw) was measured in anesthetized, 30-week-old male rats of the spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar (W) strains. The percent decrease in MAP to equivalent doses of NaNP did not differ among the three strains of rats except at 1.0 nmole/100 gbw, a dose to which W rats showed a greater depressor response than either SHR or WKY rats. Similarly, no major differences were found among the strains in their response to the administration of PGI, except to a dose of 0.1 nmole/100 gbw to which both SHR and W rats responded with a greater percent decrease in MAP than WKY rats. In contrast, the percent decrease in MAP to PGE, was generally greater in SHR than WKY rats but was found not to differ between SHR and W rats at any dose. The i.a. injection of arachidonic acid (AA), while causing dose-dependent percent decreases in MAP in all strains, produced significantly smaller hypotensive responses at doses of 10 and 100 nmoles/100 gbw in SHR as compared to WKY or W rats. At doses of 300 nmoles AA or greater, hypotensive responses did not differ significantly between SHR or WKY rats whereas the W rat exhibited percent reductions in MAP that were significantly larger than those obtained in the other two strains of rats. We conclude that SHRs do not have a reduced ability to respond to exogenous PGE PGI or NaNP; however, SHRs appear to have a decreased capacity to utilize AA for the synthesis of vasodepressor PGs.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SUMMARY We have investigated whether differences seen in the pharmacological and morphological properties of mesenteric resistance vessels from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls are also present in vessels from young SHR and WKY rats in which there is little difference in blood pressure (BP). Segments of small arteries (lumen diameter 150 $m) were taken from a specific location in the mesenteric bed of 6-, 12-, and 24-week-old SHR and WKY rats, and mounted on a myograph capable of directly measuring their tension. Vessels were set to internal circumference L, = 0.8 Lin where Ll00was an estimate of the internal circumference the vessels would have had when relaxed in situ and under a transmural pressure of 100 mm Hg. At all ages, compared with WKY vessels, the effective lumen diameter, I, = L,/x, was smaller in the SHR vessels. However, media hypertrophy was seen only in vessels from 12- and 24-week-old SHRs. In physiological salt solution the noradrenaline sensitivity of all vessels was similar (EDM* 2.4 nM). However, inhibition of neuronal uptake with cocaine revealed that at all ages the noradrenaline sensitivity of the vascular smooth muscle cells in the SHR vessels was greater than that of the cells in the WKY vessels. The results also suggested that the neuronal noradrenaline uptake was greater in the SHR vessels at all ages. The main increase in BP in the SHRs occurred between the ages of 6 week and 12 weeks. The results are therefore consistent with the hypothesis that differences in the structure of the resistance vessels are among the factors responsible for the development and maintenance of genetic hypertension. However, they point also to the possible involvement of differences in the noradrenaline sensitivity of the smooth muscle cells in the resistance vessel wails.

ISSN:0194-911X    

出版商:OVID    

年代:1980

数据来源: OVID