摘要:

Several new concepts have emerged recently regarding the effects of chronic hypertension on cerebral blood vessels. First, hypertrophy of large cerebral arteries in chronic hypertension attenuates increases in pressure of downstream vessels and protects the cerebral microvasculature. Second, In contrast to large cerebral arteries, which become less distensible during chronic hypertension, distensibility of cerebral arterioles increases during chronic hypertension despite hypertrophy of the arteriolar wall. Third, dilatation of cerebral blood vessels with disruption of the blood-brain barrier, and not vasospasm, appears to be the critical factor in the pathogenesis of hypertensive encephalopatby. This concept is supported by the finding that cerebral edema hi stroke-prone spontaneously hypertensive rats is preceded by vasodilatation and disruption of the barrier. Fourth, alterations of endotbeuum-mediated dilatation may impair vasodilator responses in chronic hypertension and predispose to ischemia. Finally, chronic hypertension impairs dilatation of collateral blood vessels hi the cerebral circulation. The implication of this finding is that increased susceptibility to cerebral infarction in chronic hypertension may be related in part to compromised responses of the collateral circulation.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

High (8%) and low (0.3%) NaCl diets were administered for 3 weeks before testing inbred Dahl salt-sensitive (SS/Jr) or salt-resistant rats (SR/Jr) for altered susceptibility to cerebral infarction after occlusion of the middle cerebral artery. At occlusion time, mean systolk blood pressure (BP) was 201 ± 7 mm Hg in SS/Jr fed a high NaCl diet. Two weeks later an atrophied infarct was present in the territory of the occluded artery of all (n= 10) hypertensive SS/Jr, and infarct size was correlated with BP at occlusion time (p< 0.01). In normotensive control SS/Jr fed a low NaCl diet (n= 11), BP (118 ± 3 mm Hg), frequency of infarction (18%), and infarct size were all significantly less (p< 0.05) than in the hypertensive rats. In SR/Jr fed a high (n= 11) or low (n= 10) NaCl diet, BP was not statistically different (112 ± 4 vs 116 ± 4 mm Hg). Cerebral infarction frequency was significantly (p< 0.05) greater in SR/Jr fed a high NaCl diet (73%) than in SR/Jr receiving a low NaCl diet (20%), but infarct size was not correlated with BP hi SR/Jr (Pgt; 0.05). Thus, elevated NaCl intake in SS/Jr and SR/Jr before middle cerebral artery occlusion predisposes to cerebral infarction, but differences in infarct size and its correlation with BP suggest the controlling factors are not identical in the two strains.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

In a previous study, we discovered that spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) are dissimilar with respect to the depressor potency differentiated between intravenously and intra-arterially infused adenosine. To test the hypothesis that this dissimilarity may reflect a difference between the two strains in adenosine transport or metabolism, we compared the kinetics of nucleoside transport (i.e., [3H]uridine uptake) in erythrocytes and the pulmonary disposition of [3H]adenosine in SHR versus WKY. [3H]Uridine uptake in rat erythrocytes was linear for 4 minutes and inhibitable with dipyridamole. Kinetic analysis (i.e., Hofstee plots) of initial uptake velocity indicated no difference between the two strains with respect to apparentKm(196 ± 40 vs 230 ± 29 μM in WKY and SHR, respectively) and maximum velocity (7.5 ± 0.4 vs 8.3 ± 0.5 pmol/2 min/12% Hct in WKY and SHR, respectively). Approximately 50% of [3H]adenosine infused into the pulmonary artery of perfused rat lung was transported into the lung, and 85% of this material was incorporated into the nucleotide pool. Radioactivity in the lung perfusate consisted initially of equal amounts of adenosine and inosine; however, within 60 seconds after administration of [3H]adenosine most of the effluent radioactivity was inosine. No differences were detected in adenosine uptake, intracellular metabolism, or extracellular metabolism in lung from SHR versus WKY. Our data indicate that any difference between SHR and WKY with respect to the biological response to adenosine cannot be attributed to differences in adenosine disposition and, therefore, must be due to pharmacodynamic differences between the strains.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Circulating digitalislike compounds have been proposed to be involved in some Na+-dependent types of experimental hypertension and in human essential hypertension. The level of circulating Na+-K+pump inhibitor(s) was investigated in the spontaneously hypertensive rat of the Okamoto strain (SHR), its normotensive control, Wistar-Kyoto rat (WKY), and the regular Wistar rat using the following criteria: the ability of whole plasma to inhibit the total active Na+efflux from Wistar rat erythrocytes and to cross-react with digoxin antibodies and the ability of plasma extracts to inhibit Na+,K+-adenosine triphosphatase (ATPase) activity of membranes from rat kidney. SHR plasma inhibited the net Na+efflux from Wistar erythrocytes by up to 27% compared with WKY or Wistar plasma. For a given number of cells, the inhibition increased with the amount of available plasma. Cross-reactivity with digoxin antibodies was twice as high in SHR as in WKY or Wistar plasma. It was already enhanced in 3- to 4-week-old rats. Plasma extracts from SHR significantly inhibited Na+,K+-ATPase activity when compared with WKY extracts (75.6 ± 2.6 vs 89.3 ± 2.4μmol P1/mg/hr;p< 0.01) but did not differ from Wistar plasma extracts. These results strongly suggest that circulating digitalislike compound(s) are present in elevated amounts in SHR as early as 3 to 4 weeks of age, but their exact participation in blood pressure elevation or maintenance remains to be clarified.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

A monoclonal antibody to α-human atrial natriuretic polypeptide (α-hANP), KY-ANP-I, has been produced by fusion of a nonproducmg mouse myeloma cell tine, X63-Ag8.653, with spleen ceDs from BALB/c mice immunized with synthetic α-hANP conjugated to bovine thyrogtobuhn using the carbodiimide coupling procedure. Hybrklomas were screened for antibody production by rarJiolmmunoassay using culture media and125I-α-hANP. They were cloned by the llmtHng dilution technique, expanded hi culture, and injected mtraperHoneaDy into BALB/c mice. The obtained antibody belonged to the immunogiobunn G1subclass. Analysis by a Scatchard plot revealed a high affinity for a-hANP, with an association constant of 3.1 x 1010M−1. With this monoclonal antibody, a specific radioimmunoassay for α-hANP has been established. The antibody in mouse ascites was available for radioimmunoassay at a final dilution of 1:106. Values of IC10and IC50in this radioimmunoassay were 3 and 30 fmol/tube, respectively. The radioimmunoassay showed a cross-reactivity of 0.9% with α-rat ANP. α-hANP-(8–22) and α-ANP-(l–6) exhibited less cross-reactivity than α-rat ANP on a molar basis. There was no cross-reaction with α-ANP-(17–28). Thus, the recognized epitope must be located in the N-terminal half of the ring structure of α-hANP including Met12residue. This radioimmunoassay could detect γ-hANP and β-hANP as well as α-hANP. The monoclonal antibody was also useful for unmunohistochemical studies. ANP-positive cells were finely stained hi the human atrium using the avidin-btotin-peroxidase complex technique. These results indicate that this monoclonal antibody to α-hANP will become a powerful tool for investigating the physiological and pathophysiological significance of ANP.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The purpose of the present study was to investigate α1-adrenergic receptors in the heart as well as the activity and the sensitivity of the phosphoinositide pathway on tissue slices of atria, ventricles, and femoral artery of hypertensive rats treated for 4 weeks with deoxycorticosterone acetate (DOCA) and 1% saline. DOCA-salt hypertensive rats were characterized by an increased sympathoadrenal tone, as suggested by increased norepinephrine and epinephrine plasma levels. The basal activity of the phosphoinositide pathway, estimated by measuring the accumulation of inositol monophosphate in the presence of an excess of lithium, was found to be greater in atria than in ventricles and femoral artery in both normotensive and DOCA-salt hypertensive rats, but it was twofold greater in atria and ventricles ofDOCA-salt hypertensive rats compared with normotensive rats. Following stimulation by norepinephrine, the production of inositol monophosphate was greater in atria and femoral artery than in ventrides in both groups. However, in DOCA-salt hypertensive rats, the production of inositol monophosphate was markedly enhanced, being about twofold greater in atria and femoral artery and about three times greater hi ventricles than hi tissues of normotensive rats. These differences between DOCA-salt hypertensive and normotensive animate do not appear to be associated with a difference in α-adrenergfc receptor number or affinity since cardiac α1-adrenergic receptor number was unchanged hi hypertensive rats and the binding affinity to the receptor was significantly decreased in hypertensive rats compared with normotensive rats. These data therefore demonstrate an increase In basal and norepinephrine-lnduced inositol monophosphate production in cardiovascular tissues of DOCA-salt hypertensive rats and suggest the existence of a hypersensitlvity of α1-adrenergic receptors or of an increased sensitivity of intracellular mechanisms responsible for the activation of the phosphatidylinositol pathway in the cardiovascular tissues of these animals.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

This study was initiated to see if the insulin resistance, hyperinsulinemia, and hypertension that follow feeding nonnotensive Sprague-Dawley rats a fructose-rich diet could be prevented by letting rats run spontaneously in exercise wheel cages. Blood pressure in sedentary rats increased from (mean ± SEM) 125 ± 2 to 148 ± 3 mm Hg in response to 2 weeks of a high fructose diet, and this increment was significantly (p< 0.001) attenuated in exercising rats (from 121 ± 1 to 131 ± 2 mm Hg). In addition, mean (±SEM) plasma insulin concentration was lower in fructose-fed rats allowed to run spontaneously (44 ± 2 vs 62 ± 5 μU/ml;p< 0.01). Finally, resistance to insulin-stimulated glucose uptake was assessed by determining the steady state plasma glucose response to a continuous glucose and exogenous Insulin infusion during a period in which endogenous insulin secretion was suppressed. The results of these studies indicated that the mean (± SEM) steady state plasma glucose concentration was significantly lower in the exercise-trained rats (127 ± 5 vs 168 ± 6 mg/dl;p< 0.001), despite tbe fact that the steady state plasma insulin levels were also lower in rats allowed to run spontaneously (75 ± 4 vs 90 ± 5 μU/ml;p< 0.05). Thus, the ability of exercise-trained rats to stimulate glucose disposal was enhanced as compared with that of sedentary rats fed the same fructose-rich diet. These data demonstrate that the insulin resistance, hyperinsulinemia, and hypertension produced hi nonnotensive rats by feeding them a high fructose diet can be attenuated if rats are allowed to run spontaneously. These results provide further support for the hypothesis that insulin resistance and hyperinsulinemia play a role in the pathogenesis of fructose-induced hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

This study was undertaken to determine what factors might contribute to arterial supersensitivity to norepinephrine associated with deoxycorticosterone acetate (DOCA)-sait hypertension in the rat. Experimental groups of male rats were uninephrectomized and 1 week later began receiving twice weekly Injections of DOCA (20 mg/kg s.c. in sesame oil) plus 1% NaCl and 0.2% KC1 in their drinking water. For each experimental group, a group of age-matched male rats underwent a sham operation and received injections of sesame oil and the NaCl-KCl drinking water. Perfused caudal arteries from 3- week-hypertensive rats were supersensitive to intraluminal and extraluminal norepinephrine administration. However, this difference hi sensitivity between hypertensive and control caudal arteries was demonstrable at low rates of perfuslon, 0.5 to 1.0 ml/min, but not at rates of 2.0 to 2.6 ml/min. The supersensitivity was not due to differences hi neuronal uptake or to inhibition of extraneuronal uptake by DOCA. The perfused mesenteric vascular bed from 3- or 6-week-hypertensive rats was also supersensitive to intraluminal norepinephrine. However, the demonstration of supersensitivity hi the mesenteric vasculature was independent of perfusion rate (2.3–6.8 ml/min) and perfusion pressure in the range of 30 to 60 mm Hg. There was little or no supersensitivity to transmural nerve stimulation hi either the caudal artery or the mesenteric vasculature, a finding consistent with the observed decrease hi endogenous norepinephrine content. Microelectrodes were used to determine resting membrane potential hi the smooth muscle cells. No differences hi resting membrane potential were detected between caudal or mesenteric arteries from hypertensive compared with control rats 2, 3, or 6 weeks after initiation of the DOCA-salt regimen. It is concluded that 1) the perfusion rate is a critical factor hi designing experiments to test the sensitivity of caudal arteries to drugs, 2) the perfused mesenteric vascular bed is a useful preparation for studying sensitivity of blood vessels hi hypertension, 3) the supersensitivity of blood vessels hi the DOCA-salt model may be of greater importance relative to circulating catecholamines than to sympathetic innervation, and 4) the supersensitivity of blood vessels to norepinephrine in the DOCA-salt model is not due to changes in neuronal uptake, extraneuronal uptake, or membrane potential of the vascular smooth muscle cells.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The contribution of alterations in renal hemodynamics to the diuretic and natriuretic actions of atrial natriuretic factor (ANT) was studied in chronically instrumented conscious dogs. Injection of ANF-(99–119), 10 μg/kg, had no effect on mean arterial pressure, heart rate, renal blood flow, or calculated renal vascular resistance; However, it increased urine flow rate (86 ± 20%) and sodium (118 ± 24%) and potassium (35 ± 22%) excretion (p< 0.05). In contrast, ANF-(99–122), 10 /ig/kg, significantly increased renal blood flow (26 ± 4.5%), reduced renal vascular resistance (24 ± 2.9%) and arterial pressure (5.5 ± 1.9%), and markedly increased urine flow rate (198 ± 34%) and sodium (206 ± 32%) and potassium (75 ± 27%) excretion (p< 0.05), being almost twice as effective in the first 10 minutes as was ANF-(99–119) infusion. During a brief infusion, ANF-(99–122) (10 fig/ kg/min for 4 minutes) increased renal blood flow (24 ± 2.7%), heart rate (18 ± 5.7%), urine flow rate (199 ± 25%), and sodium (290 ± 81%) and potassium (104 ± 17%) excretion. Injection of radioactive microspheres (15 or 9 μm) to measure intrarenal distribution of blood flow during the steady state increase in renal blood flow indicated that ANF-(99–122) infusion preferentially increased outer cortical blood flow. Blood flow in the four zones of the kidney cortex (Zone 1, outer, and Zone 4, inner) increased 96 ± 25% (Zone 1), 199 ± 87% (Zone 2), 139 ± 47% (Zone 3),p< 0.05, and 25 ± 28% (Zone 4,p= NS). Infusion of ANF-(99–119) did not lead to a redistribution of renal cortical blood flow as seen with ANF-(99–122). During a 1-hour infusion of ANF-(99–122), renal blood flow increased only transiently whereas glomerular filtration rate, urine flow rate, and sodium and potassium excretion increased 118 ± 15%, 104 ± 6.8%, 144 ± 24%, and 115 ± 26%, respectively. Following α-adrenergic receptor blockade, infusion of ANF-(99–122) resulted in renal vasodilation for the duration of the study. Therefore, In conscious dogs, ANF-(99–119) and ANF-(99–122) both enhance renal function while ANF- (99–122) also increases renal blood flow. Although not essential, the ANF-induced renal vasodilation accentuates and hastens the initial diuresis and natriuresis, thereby increasing the total salt and water excretion.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Our previous studies support the hypothesis that activation of the renin-angiotensin system by renal ischemia elevates adenosine levels and that adenosine acts in a negative feedback loop to limit renin release and to mitigate some of the hypertension-producing effects of angiotensin II. To further test this hypothesis, we compared the time course of caffeine-induced Increases in plasma renin activity with the time course of changes in plasma levels of adenosine in two models of renin-dependent renovascular hypertension. Also, we compared the effects of caffeine on plasma renin activity and arterial blood pressure in renin-dependent versus renin-independent renovascular hypertension. In comparison to sham-operated rats, plasma levels of adenosine In the left and right renal veins and aorta were elevated severalfold in two-kidney, one clip rats (2K1C) 1 week after left renal artery clipping. However, adenosine levels declined during the second and third weeks after clipping. In 2K1C rats treated chronically with caffeine, plasma renin activity was markedly elevated during the first week after operation as compared to non-caffeine-treated 2K1C rats. However, during the second and third weeks after clipping, caffeine had lesser effects on plasma renin activity. A temporal relationship between plasma adenosine levels and caffeine-induced hyperreninemia was also observed in rats with aortic ligation. Caffeine accelerated hypertension in 2K1C rats and rats with aortic ligation (renin-dependent renovascular hypertension), but it had no effect on plasma renin activity or blood pressure hi one-kidney, one clip rats (renin-independent renovascular hypertension). These results lend further support to the hypothesis that adenosine functions to mitigate the renin-angiotensin system hi renin-dependent renovascular hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID