ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

For the general practitioner to be able to prescribe optimal therapy to his individual hypertensive patients, he needs accurate information on the therapeutic agents he is going to administer and practical treatment strategies. The information on drugs and drug combinations has to be applicable to the treatment of individual patients and not just patient study groups. A basic requirement is knowledge of the dose-response relationship for each compound in order to choose the optimal therapeutic dose. Contrary to general assumption, this key information is difficult to obtain and often not available to the physician for many years after marketing of a drug. As a consequence, excessive doses are often used. Furthermore, the physician needs comparative data on the various antihypertensive drugs that are applicable to the treatment of individual patients. In order to minimize potential side effects due to unnecessary combinations of compounds, the strategy of sequential monotherapy is proposed, with the goal of treating as many patients as possible with monotherapy at optimal doses. More drug trials of a crossover design and more individualized analyses of the results are badly needed to provide the physician with information that he can use in his daily practice. In this time of continuous intensive development of new antihypertensive agents, much could be gained in enhanced efficacy and reduced incidence of side effects by taking a closer look at the drugs already available and using them more appropriately in individual patients.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Neuropeptide Y is known to enhance blood pressure responsiveness to various constrictors, including angiotensin II, and to suppress renin secretion. This study was undertaken to assess the effect of neuropeptide Y on the development of two-kidney, one clip renal hypertension. Normotensive rats either had a silver clip placed on the left renal artery or were sham-operated upon. An osmotic minipump, which was connected via a catheter to a jugular vein, was implanted subcutaneously in all rats. These pumps delivered either neuropeptide Y (0.001 ug/min) or saline intravenously. Eight days later, an intra-arterial catheter was inserted and the rats were studied while not anesthetized on the following day. Neuropeptide Y did not affect body weight. In clipped rats, neuropeptide Y prevented the development of hypertension and suppressed renin secretion. Neuropeptide Y significantly decreased blood pressure also in sham-operated rats, although it had no effect on plasma renin activity. These data indicate that prolonged neuropeptide Y infusion may lower blood pressure by different mechanisms, one of which is probably a suppression of renin release.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Adrenocorticotrophin (ACTH) administration has been systematically studied in man and sheep. It raises systolic blood pressure (SBP) in the rat, but this has been little studied. ACTH was injected once daily at 0.5 mg/kg for 12 days in male Sprague-Dawley rats (n=19). Sham-injected animals were studied in parallel (n=15). ACTH increased SBP from 94 ± 4 to 121 ± 4mmHg (P < 0.001), significantly greater (P < 0.02) than sham injection. The SBP of ACTH-treated rats was significantly higher than that of sham-injected rats when the same animals were measured by both the tail-cuff method (ACTH, 126 ± 3mmHg; sham, 99 ± 3 mmHg) and direct arterial cannulation (ACTH, 137 ± 2 mmHg; sham, 123 ± 3 mmHg): P<0.005 and P<0.001, respectively. There was a loss of body weight, and increased water intake and urine output in ACTH-treated animals compared with both control (P < 0.001) and sham treatments (P < 0.02). ACTH increased plasma [Na] (sham, 140 ± 1 mmol/l; ACTH, 145 ± 1 mmol/l; P < 0.001) and urinary Na excretion compared with control (P < 0.01) and sham injection (P < 0.05), and also decreased plasma [K] (sham, 4.6 ± 0.2 mmol/l; ACTH, 3.3 ± 0.8 mmol/l; P < 0.01) and increased urinary K excretion (P < 0.01) compared with control. SBP in adrenalectomized animals (n=10) was unchanged by ACTH. ACTH increased adrenal, renal, cardiac and brain weights compared with sham injection (P < 0.05). There were no significant changes in vascular morphology, although ACTH treatment increased glomerular epithelial cell droplets and abolished the adrenal zona glomerulosa.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Although alterations in Ca2 +metabolism have been demonstrated in subcultured aortic myocytes of spontaneously hypertensive rats (SHR), changes in intact tissue have not been described. This study compares Ca2 +metabolism in intact mesenteric resistance arteries and in myocytes that were derived from mesenteric arteries and maintained in primary and long-term culture. Using fura-2, basal levels of Ca2 +were found to be similar in intact vessels of SHR and Wistar-Kyoto normotensive rats (WKY), and in primary and first-passage myocytes of the two strains. During subculture, basal levels of Ca2+became elevated in myocytes of SHR. When norepinephrine-induced Ca2+mobilization was examined, the threshold of resistance arteries was lower in SHR, but differences were not detected with higher concentrations of the agonist. Norepinephrine-induced Ca2+mobilization also did not differ between primary myocytes of the two strains. Angiotensin II elicited greater intracellular Ca2 +responses in myocytes of SHR at passages 1, 3 and 5. Cell growth was assessed at each passage level. While no strain differences were detected in primary, first- and second-passage cells, the growth rate became elevated in SHR in subsequent passages. These results are consistent with the hypothesis that vascular myocytes cultured from SHR with established hypertension exhibit differences in Ca2+metabolism that are not present in the intact vessel wall. Furthermore, intracellular Ca2+appears to be elevated in myocytes of SHR when the rate of proliferation is increased.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Testosterone, a steroid hormone which increases blood pressure by hitherto unknown mechanisms, is known to induce renin synthesis in the submandibular gland (SMG) of mice. Since renin as well as all other components of the renin-angiotensin system are present in organs important for cardiovascular control, e.g. the kidney, heart, adrenal gland and brain, it is of interest to study the effect of testosterone on renin gene expression in these organs. Renin messenger (m) RNA concentrations were measured by a solution hybridization assay using a 32P-labeled mouse SMC renin complementary (c) RNA as a radioactive probe (detection limit: 1 pg renin mRNA). Measurements were performed after 2h and after 2, 7, 14 and 21 days of dihydrotestosterone (DHT) treatment in female NMRI mice. Renin mRNA concentration (values are expressed as pg renin mRNA/ (ig total RNA) in the SMC was significantly increased after 7 days (108 ± 22 in controls versus 630 ± 101 in DHT-treated mice), after 14 days (83 ± 15 in controls versus 743 ± 83 in DHT-treated mice) and after 21 days (107 ± 30 in controls versus 579 ± 76 in DHT-treated mice), but did not reach levels found in untreated male NMRI mice (1021 ± 84). In the kidney, a decrease was observed within 21 days, from 43 ± 4 and 40 ± 4 to 29 ± 2 and 22 ± 1.7pg/|ig in controls and DHT-treated groups, respectively. Values in male mice were 22.5 ± 2.5 pg/ug. In the adrenal glands, we found an immediate increase in renin mRNA concentration after 2h (5.8 ± 1.3pg/ug in controls versus 22.1 ± 2.2pg/ug in DHT-treated mice) and after 2 days (9.9 ± 0.9pg/(ig in controls versus 21.2 ± 3.0pg/|ig in DHT-treated mice). In the brain, renin mRNA concentration increased after 21 days from 0.21 ± 0.01 (controls) to 0.37 ± 0.026 pg/ng after DHT treatment. Our measurements provide evidence for a tissue-specific regulation of renin mRNA by DHT in several organs important for blood pressure control. Moreover, the early increase in renin mRNA in the adrenal gland and the late rise in the brain observed after DHT treatment are of interest in view of the possible importance of renin for steroid synthesis and central cardiovascular control.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In order to investigate the involvement of endothelium-derived vasoactive substances in deoxycorticosterone acetate (DOCA)-salt hypertension, the responses to noradrenaline, acetylcholine, sodium nitroprusside and papaverine were studied in the absence and presence of indomethacin. Noradrenaline was equally effective in evoking a constrictor response of aorta, with or without endothelium, isolated from DOCA-salt hypertensive rats, while in controls, noradrenaline induced higher submaximal responses in rubbed than in unrubbed preparations. A decreased response to acetylcholine, an endothelium-dependent vasodilator, was observed in aorta with endothelium which had been precontracted with noradrenaline isolated from hypertensive rats. The relaxant response was lost after removal of the endothelium in both control and DOCA-salt hypertensive groups. The response to sodium nitroprusside, an endothelium-independent agent, in aorta isolated from hypertensive rats as well as the response to papaverine, an agent partially dependent on the endothelium, was not altered. Indomethacin treatment altered the response to noradrenaline only in unrubbed aorta of hypertensive rats. In these preparations, a biphasic response to noradrenaline was observed. At lower concentrations noradrenaline induced the characteristic constrictor response, while at higher concentrations a relaxant response was obtained that was abolished by methylene blue, a guanylate cyclase inhibitor. This could indicate that noradrenaline induced the release of endothelium-derived relaxing factor (EDRF) in aorta of hypertensive rats. Furthermore, indomethacin treatment restored the decreased response to acetylcholine in aorta isolated from DOCA-salt hypertensive rats. It is suggested that DOCA-salt hypertension causes an impaired response to acetylcholine and an increased response to noradrenaline in aorta because of an alteration of some endothelial cell function which is not related to a diminished release and/or production of EDRF, but to a simultaneous release of an endothelium-derived contracting factor (EDCF) which is sensitive to indomethacin blockade.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID