ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The possible role of the renin-angiotensin system in the maintenance of hypertension in two-kidney, one clip hypertensive rats was studied. Plasma renin activity rose rapidly and markedly in association with the elevation of blood pressure and then decreased gradually, although blood pressure remained high. Renin activity in the lung, aorta, and mesenteric artery also increased with the development of hypertension and then decreased in a way similar to that of plasma renin activity at the chronic stage of hypertension. Plasma angiotensin converting enzyme activity did not change significantly until 16 weeks after unilateral renal artery clipping, whereas vascular angiotensin converting enzyme activity significantly increased at the chronic, but not the acute, stage of hypertension. In chronically renal hypertensive rats, 1-sarcosine, 8-isoleucine angiotensin II or enalapril, an angiotensin converting enzyme inhibitor, lowered the blood pressure and enalapril also lowered the angiotensin converting enzyme activity of vascular tissues. The constrictor effect of angiotensin I was greater in isolated arteries from chronically hypertensive rats than in those from age-matched normotensive rats. These results suggest that the vascular renin-angiotensin system plays an important role in the maintenance of two-kidney, one clip hypertension. Elevated vascular angiotensin converting enzyme activity appears to increase local production of angiotensin II, which results in vasoconstriction by acting directly and indirectly through adrenergic nerves on vascular smooth muscle.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Development of hypertension in Dahl salt-sensitive rats (DS) is accompanied by reduced renomedullary prostaglandin synthesis, which may be responsible for their lower natriuretic capacity. To examine the changes in renomedullary prostaglandin E2synthesis, the effects of high (8.0%) and normal (0.6%) NaCl diets were examined in DS and in Dahl salt-resistant rats (DR). In response to an 8.0% NaCl diet, the number of prostaglandin E2receptors in the renal outer medulla of DR increased (2.97 ± 0.2 vs 2.18 ± 0.2 pmol/mg on 0.6% NaCl diet) while no change was noted in their affinities (Ka, 9.5 ± 0.2 vs 9.4 ± 0.3 nM). Receptor number and affinity in the renal cortex, inner medulla, and liver of DR were not affected. In contrast, renomedullary receptors of DS had a lower affinity than those of age-matched DR (KA, 13.9 ± 0.2 nM on 0.6% NaCl diet and 14.0 ± 0.3 nM on 8.0% NaCl diet) and did not increase in number after a high salt diet. This apparent inability of DS to modulate prostaglandin receptors may contribute to their susceptibility to salt-induced hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Blood pressure and parameters of sodium balance were measured during the first 16 weeks of life in male Okamoto spontaneously hypertensive rats (SHR,n= 22), Wistar-Kyoto rats (WKY,n= 25), and the F, (n = 27) and F2(n = 81) hybrids of the SHR and WKY. Genetic analysis revealed that blood pressure in SHR was controlled by approximately four independent genetic loci and the degree of genetic determination was 64.5%. No difference in blood pressure was discernible before 12 weeks of age between those F2rats that at 16 weeks had blood pressures either higher or lower than one standard deviation from the mean. Exchangeable sodium was measured sequentially in individual rats of all populations by determining their whole-body radioactivity while receiving 37.5 mM 22Na/23NaCI drinking fluid of constant specific activity as their sole source of sodium. The SHR had consistently higher exchangeable sodium levels than WKY and showed evidence of relative sodium retention during the early developmental phase of hypertension. Sodium intake was higher in SHR than WKY from 4 to 16 weeks of age, although saline preference was the same in both strains. None of these parameters of sodium balance were found to correlate with blood pressure in the F2population. It is concluded that the hereditable abnormalities of sodium balance in SHR appear to represent coincidental inbred characteristics controlled by genetic loci that are unrelated to those loci responsible for the expression of hypertension in this model.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to investigate the adaptive biochemical changes in the myocardium in response to chronic afterload. Ouabain-inhibited Na+, K+-adenosine triphosphatase (ATPase) activity was decreased by 40% in myocardium of SHR compared with that from WKY, which may lead to increased intracellular Ca2+through Na+-Ca2+exchange. Similarly, α1-adrenergic receptor density, estimated by [3H]prazosin binding, was decreased by 42% in myocardial membranes of SHR, while the affinity for the agonist and the antagonist was not altered. In contrast, the number of Ca2+channels estimated by [3H]nitrendipine binding was increased by 45% in myocardial membranes of SHR, while the affinity was comparable between SHR and WKY. These differences between WKY and SHR in the membrane properties were not due to differential contamination of plasma membranes because the activities of other putative plasma membrane marker enzymes were comparable between WKY and SHR. There were no differences between WKY and SHR in the myosin ATPase activity estimated using myofibrils, actomyosin, and myosin. These results suggest that specific alterations have occurred in the plasma membrane properties of myocardium of SHR that result in altered intracellular Ca2+metabolism. These alterations may have an important bearing on excitation-contraction coupling in myocardium of SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The transport and distribution of sodium, potassium, and water were examined in tail arteries of rats treated with deoxycorticosterone acetate (DOCA)-saline for 10 days, a time that marks the earliest onset of a rise of blood pressure in the strain (Wistar) used. The arteries were incubated for more than 20 hours to ensure that any change observed was sufficiently built in so that it could not readily be washed out. Three distinct changes were observed. First, the steady state transmembrane sodium gradient (operationally [NaVfNa],) was increased. Second, the amount of sodium excluded from participation in the sodium gradient, and hence probably bound, was increased. Third, after prolonged potassium depletion, the ouabain-insensitive loss of cell water and sodium that follows the readmittance of potassium was increased. These results suggest that fundamental embedded changes in sodium transport occur well before the blood pressure rises in response to DOCA-saline.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The in vivo effects of two anti-human renin monoclonal antibodies with a high binding affinity for primate renin were studied in conscious, volume-depleted marmosets. These antibodies, R-3–17–7 and R-3–36–16, both have high binding activity for renin, but only R-3–36–16 inhibits the enzymatic activity of renin in vitro. In vivo, R-3–17–7 did not affect blood pressure after intravenous injection of doses up to 100 jug/kg, although plasma renin activity was partially reduced. In contrast, R-3–36–16 induced a reduction in blood pressure and an inhibition of plasma renin activity at a threshold dose of 3 ftg/kg. The maximum fall in blood pressure and complete inhibition of plasma renin activity were observed after R-3–36–16, 10/i-g/kg; these effects persisted for up to 2 hours. Pretreatment with a converting enzyme inhibitor or nephrectomy prevented the hypotensive effects of R-3–36–16. Conversely, pretreatment with R-3–36–16 prevented the hypotensive effects of a converting enzyme inhibitor. These findings indicate that the hypotensive response induced by R-3–36–16 is due entirely to blockade of the renin-angiotensin system. Thus, R-3–36–16 appears to be a specific, potent, and long-acting inhibitor of primate renin. Such monoclonal antibodies provide interesting tools for studying the effects of acute and chronic renin blockade.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of synthetic atrial natriuretic factor and atriopeptin III on induced tone in resistance-sized arteries from the rat were examined in vitro. Cylindrical segments of small mesenteric or cerebral arteries were mounted on a microcannula and pressurized to a transmural pressure of 75 mm Hg. After equilibration, the level of tone in cerebral arteries was on the order of −35 % change in diameter; addition of atrial natriuretic factor or atriopeptin III in cumulative doses from 10−10to 10−7M did not produce any transient or sustained changes in diameter. Similarly, atrial natriuretic factor or atriopeptin III did not alter the contractile responses of cerebral vessels to serotonin or prostaglandin F1. Mesenteric arteries, which do not possess an intrinsic myogenic tone, were precontracted with potassium (30 mM), norepinephrine (10−6M), or prostaglandin F1(1.1 × 10−5M) and exposed to the synthetic natriuretic peptides, also without effect. Transmural electrical stimulation (0.3-msec pulses; 180 mA; 4/second) relaxed cerebral and contracted mesenteric arteries; preincubation in 10−7M atrial natriuretic factor or atriopeptin III did not alter subsequent responses. These observations suggest that the hypotensive action of atrial natriuretic factor cannot be attributed to direct vasodilation of splanchnic or cerebral resistance-sized arteries.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To define the mechanisms whereby clonidine lowers blood pressure, we measured cerebrospinal fluid and plasma levels of norepinephrine, normetanephrine, epinephrine, dopamine1and the dopamine metabolite homovanillic acid in 10 primary hypertensive subjects before and after 3 months of clonidine treatment (mean dose, 0.68 mg/day). Catecholamines were measured by radioenzymatic methods. Cerebrospinal fluid and plasma sampling was performed after subjects had fasted and remained supine overnight, and plasma sampling was repeated 2 hours later, after subjects had ambulated. Supine and upright blood pressure fell, as might be expected. Cerebrospinal fluid levels of norepinephrine and normetanephrine fell significantly, but dopamine and homovanillic acid levels were unchanged. Plasma norepinephrine, normetanephrine, and epinephrine levels decreased 30 to 50%, and supine dopamine levels also fell. The percent fall in supine blood pressure was related to the fall of cerebrospinal fluid and plasma norepinephrine. There were also positive relationships between the decreases of plasma norepinephrine and of normetanephrine and dopamine. The cerebrospinal fluid/plasma norepinephrine ratio was unaffected by clonidine, suggesting that the drug lowered both pools equally. Our findings indicate that clonidine decreases both central and peripheral norepinephrine activity. The dopaminergic activity of cerebrospinal fluid was unaffected by clonidine, and though plasma dopamine levels tended to be lower after treatment, mean plasma prolactin level, an index of dopaminergic activity, was also unchanged. The fall in plasma epinephrine level is probably related to diminished sympathetic adrenomeduilary stimulation and is unlikely to contribute to clonidine's antihypertensive action. These results also suggest that measurement of normetanephrine in cerebrospinal fluid and plasma provides a good index of norepinephrine activity.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID