摘要:

Phospholipase A2activity, pbospholipids, and phospholipid fatty acids were investigated in renal membrane of male stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto rats. Renal phospholipase A2activity increased and membranous phospholipids, especially phosphatidylchoUne and phosphatidylethanolamine, decreased with age in SHRSP. Arachidonate in phospholipid also decreased with age in SHRSP. To determine the effect of pressure load on the lipid alterations in renal membrane, SHRSP that received antihypertensive treatment with hydralazine, enalapril, or nicardipine for 5 weeks were compared with those without treatment. Antihypertensive treatments prevented phospholipid degradation and increased arachidonate in phospholipid relative to the control group. Phospholipase A2 activity in each group treated with antihypertensive drugs did not differ from that in the control group. These results suggest that the course of hypertension causes renal membranous phospholipid degradation and increases phospholipase A2activity. Antihypertensive treatments may prevent these lipid alterations in SHRSP. These renal membranous structural changes may provide an explanation not only for functional abnormalities such as decreased membrane fluidity but also for the progress of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Direct effects of dopamine on renin release were examined using static incubations and perifusions of rat renal cortical slices. Dopamine (10−5M) significantly stimulated renin release compared with control. To determine which receptors are involved in dopamine-elicited renin release, studies were performed with specific dopamine-1 and dopamine-2 receptor agonists and antagonists, as well as with α- and β-adrenergic antagonists. Fenoldopam, a dopamine-1 receptor agonist, dose dependently stimulated renin secretion both in static incubations and perifusions; whereas quinpirole (10−7-10−5M), a dopamine-2 receptor agonist, was ineffective. Phentolamine (10−4M), an a-adrenergic antagonist, did not alter dopamine- or fenoldopaminduced renin release. Similarly, propranolol, a β-blocker, did not interfere with the renin stimulation of dopamine (10−5M) or fenoldopam (10−6M) in incubations or perifusion experiments; whereas propranolol significantly blocked isoproterenol action. SCH 23390 (10−5M), a specific dopamine-1 antagonist, blocked dopamine- and fenoldopam-induced renin. In contrast, pimozide, a dopamine-2 receptor antagonist, was ineffective. These studies indicate that dopamine is a direct renin secretogogue, and its effects seem to be mediated by specific dopamine-1 receptor activation, as neither α- nor β-adrenergic blockers nor dopamine-2 receptor antagonists altered dopamine actions. The results suggest that dopamine produced locally in the kidney may stimulate renin secretion directly by dopamine-1 receptor activation.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Secretory components of the adrenal medulla were compared in normotensive Wistar-Kyoto (WKY) rats and in stroke-prone spontaneously hypertensive rats (SHRSP) at both 4 and 12 months of age. Noradrenaline, adrenaline, dopamine, neuropeptide Y, and chromogranins A and B were significantly higher in adrenal glands of SHRSP than those of WKY rats at 4 months. At 12 months, the levels of these components in SHRSP had increased even more (about 200% in WKY rats). There was no change in the relative composition of the adrenal “secretory cocktail”. Neither the chromogranin A/chromogranin B ratio nor their apparent proteolytic processing in chromaffin granules differed between SHRSP or WKY rats. The lack of a significant change in membrane-bound cytochrome b561and the small increase in dopamine β-hydroxylase suggest that the higher levels of secretory components in SHRSP are not simply caused by an increase in the number of chromaffin granules, but possibly by a selective increase in the secretory content of these organelles providing a larger package for quantal release by exocytosis. This may be relevant for the elevation of blood pressure in this strain. The immunological methods described in this paper allow for the first time a determination of the secretory quantal levels in catecholamine storage. This should be useful for further studies in hypertensive models.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Long-term regulation of blood pressure in a hypertensive rat may be mediated by elevated DNA content of smooth muscle cells of resistance vessels. This study explores DNA changes represented by an increased frequency of polyploid cells in multiple levels of the mesenteric arterial tree of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) control rats. Two ages were examined: 45 and 78–80 weeks of age. SHR and WKY rats did not differ in frequency of polyploid cells at any mesenteric branch level at either age. Although hypertension per se seemed not to be a factor, both species showed increased numbers of polyploid cells with aging at certain branch levels of the mesenteric arterial tree. The data in the current study support the idea that hypertension and aging may result in similar and possibly additive changes in DNA in the vessel wall.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A chemomechanical study of hypertrophied hearts of 6-month-old spontaneously hypertensive rats (SHR) and that of age-matched Wistar-Kyoto (WKY) rats was carried out, analyzing the response of the heart to steady-state changes in coronary perfusion pressure. The ratio of heart (dry)-to-body (wet) weight of WKY rats was 0.37±0.02 (103) and for SHR was 0.58±0.03 (10−3) (p< 0.01). In the apex-ejecting, isolated, pyruvate-perfused working hearts of WKY rats and SHR, coronary flow was constant when coronary perfusion pressure was set between 140 and 190 cm H2O (range of autoregulation). Coronary flow was perfusion pressure dependent when the coronary perfusion pressure was set below 110 cm H2O for both WKY rats and SHR. Cardiac output, developed pressure, rate of pressure development (dP/dt), and oxygen consumption were constant in the range of autoregulation but decreased in the direction of coronary flow when coronary flow was reduced by a drop in perfusion pressure. Similarly, the phosphorylation potential, phosphocreatine, adenosine triphosphate, and cyclic adenosine monophosphate were constant in the range of autoregulation but decreased directionally with coronary perfusion pressure below 110 cm H2O for both SHR and WKY rats. There was a significantly lower phosphorylation potential in SHR as compared with WKY rats when coronary perfusion pressure was reduced to 80 cm H2O. In the region of autoregulation, coronary flow and oxygen consumption were significantly less in SHR, although developed pressure was significantly greater at both high and low workloads. The importance of coronary perfusion pressure in SHR using the apex-ejecting working heart model was confirmed using other isolated perfused heart models (i.e., the Langendorff apex-vented heart model to simulate low workloads and the Langendorff isovolumic heart model to simulate high workloads). Furthermore, findings were not changed if FC-43 was added to the perfusate to facilitate delivery of oxygen to the myocardium and increase the viscosity of the perfusate.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

EXP6155 (2-n-butyl-l-[4-carboxybenzyl]-4-chloroimidazole-5-acetic acid) and EXP6803 (methyl 2-n-butyl-l-[4-(2-carfooxybenzamido)ben2yl]-4-chloroimidazole-5-acetate, sodium salt) are shown to be novel, nonpeptide, antihypertensive, specific angiotensin II receptor antagonists. In rabbit aorta, they competitively inhibited the contractile response to angiotensin II with pA2values of 6.54 and 7.20 and did not alter the response to norepinephrine or KC1. In guinea pig ileum, both agents blocked the responses to angiotensin I and II and did not alter the responses to bradykinin and acetylcholine. A similar specific angiotensin II antagonism was shown in vivo in the spinal pithed rat model. In renal artery-ligated rats, a high renin hypertensive model, EXP6155 and EXP6803 given intravenously, decreased blood pressure with ED30of 10 and 11 mg/kg, respectively. Both compounds did not alter blood pressure when given orally at 100 mg/ kg. Unlike saralasin, EXP6155 and EXP6803 given intravenously did not cause a transient increase in blood pressure in the renal artery-ligated and nonnotensive rats. Our results indicate that EXP6155 and EXP6803 are selective angiotensin II receptor antagonists and antihypertensive agents. Since neither compound had partial agonist activities or bradykinin potentiation effects, unlike the existing peptide angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors, respectively, they may represent preferred probes for studying the physiological roles of angiotensin II.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

No. Abstract

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID