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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular hypertrophy plays an important role in the development and maintenance of hypertension. Hyperactivity of the sympathetic nervous system may be one of the initiating factors responsible for the stimulation of growth processes involved in these structural alterations. We have used a well-established early biochemical marker of cellular growth processes, induction of ornithine decarboxylase (ODC), to determine whether alpha 1-adrenergic receptor-induced vascular trophic responses are dependent on arterial pressure elevation. Hydralazine or felodipine were coadministered to control the alpha 1-adrenergic receptor agonist-induced rise in mean arterial pressure (MAP). Methoxamine (2, 5, or 10 mg/kg s.c.) increased the average MAP (up to 20 mm Hg) and vascular ODC activity (up to ninefold) above control rats over 4 hours. Concomitant administration of hydralazine (0.5, 1.25, or 5 mg/kg s.c.) or felodipine (100 or 250 micrograms/kg s.c.) with methoxamine (10 mg/kg) attenuated the alpha 1-adrenergic receptor-induced activation of ODC in the aorta and mesenteric resistance vasculature, as well as the MAP increases. Vasodilators alone did not lower basal vascular ODC activity. The major findings include: 1) alpha 1-adrenergic receptor activation dose-dependently induces vascular ODC activity concomitantly with MAP elevation, 2) vasodilators inhibited both the alpha 1-adrenergic receptor-induced MAP increases and the activation of mesenteric vascular and aortic ODC, and 3) the stimulus-response correlation between MAP elevation and mesenteric (r = 0.78) and aortic (r = 0.92) ODC activation was characterized by a logistic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Dec
PMID:Vasodilators inhibit acute alpha 1-adrenergic receptor-induced trophic responses in the vasculature. 136 Apr 48

Chronic continuous infusion of norepinephrine in rats causes alterations in biochemical and physiologic responses of the cardiovascular system and in cardiovascular adrenoceptor number. The response of cardiac and aortic ornithine decarboxylase (ODC) activity to stimulation by norepinephrine was decreased in rats receiving norepinephrine infusion. These responses are due to stimulation of beta- and alpha-adrenergic receptors, respectively. Additionally, there was reduced stimulation of aortic ODC activity by angiotensin II and vasopressin. The cardiac ODC response to angiotensin II was decreased, but the response to vasopressin was not affected. The decreased ODC response is accompanied by decreased pressor responses to the alpha-adrenergic agonist phenylephrine. Decreased numbers of alpha- and beta-adrenoceptor binding sites (as measured by the binding of [3H]prazosin and [125I]pindolol) might mediate, in part, the altered responses to adrenergic agonists. The decreased cardiovascular responsiveness measured in these animals after several days of norepinephrine infusion hypertension contrasts with the increased responses found in most other forms of hypertension. This provides a useful model in which to examine the consequences of prolonged adrenergic receptor stimulation.
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PMID:Alterations in cardiovascular responsiveness and adrenoceptor binding during catecholamine infusion hypertension in rats. 185 May 25

This study was performed to determine if an alteration in vascular polyamine contents is associated with the development of deoxycorticosterone acetate-salt hypertension. The effects of chronic administration of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase and thus polyamine biosynthesis, on vascular polyamine contents, structure, and function as well as the development of hypertension was studied. Control and deoxycorticosterone acetate-salt rats received either tap water or a drinking solution containing alpha-difluoromethylornithine for 6 weeks, during which period systolic blood pressures were recorded. Vascular reactivity studies were performed on rings of aorta and tail artery. Medial thickness, vessel weight, and vascular polyamine contents were also assessed in these arteries. alpha-difluoromethylornithine treatment had no significant effect on either systolic blood pressure or vascular structure, function, and polyamine contents of control animals. The elevation in blood pressure and the increase in medial thickness, ring weight, and vascular polyamine contents as well as altered vascular reactivity observed in deoxycorticosterone acetate-salt rats was significantly attenuated by alpha-difluoromethylornithine treatment. These results are the first to demonstrate that vascular polyamine contents are elevated in the deoxycorticosterone acetate-salt rat and that chronic alpha-difluoromethylornithine treatment prevents the rise in vascular polyamines as well as the elevation in blood pressure and attendant changes in the vasculature. Thus, the increase in vascular polyamines may comprise a critical link between the initiating stimuli and the alterations in vascular structure and function implicated in the pathogenesis of deoxycorticosterone acetate-salt hypertension.
Hypertension 1991 Jul
PMID:Polyamines, vascular smooth muscle, and deoxycorticosterone acetate-salt hypertension. 186 Jul 16

Previous studies from our own and other laboratories have shown that hypertension induces changes in the growth of arterial smooth muscle cells (SMC). The purpose of this study was to examine the role of ornithine decarboxylase (OrnDCase) in this process. OrnDCase, the rate limiting enzyme in polyamine biosynthesis, increases in activity early in the cell cycle, and has been used as a marker of cell growth or proliferation. Deoxycorticosterone (DOC)/salt hypertension was induced in male Wistar rats. At 1-3 day intervals of DOC/salt treatment, the aortas were removed and OrnDCase activity and DNA content were determined. The results indicated that OrnDCase activity increased as early as day 2 of DOC/salt administration, reached a peak at day 10, and fell to a baseline by day 16. DNA content increased after day 10 to levels approximately 25% greater than in controls. Significant increases in blood pressure were not observed until after day 8. The findings indicate that OrnDCase activity is stimulated by DOC/salt even before the rise in blood pressure and that factors other than blood pressure per se may be important in stimulating aortic smooth muscle cell growth in the development of hypertension.
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PMID:Aortic ornithine decarboxylase activity in deoxycorticosterone/salt hypertensive rats. 199 88

Clonidine (CLON), an alpha-2 adrenergic agonist, is widely used to reduce hypertension; it is also recommended for blocking acute opiate withdrawal. Lofexidine (LOF), a CLON analog, is an investigational compound being readied for the marketplace. Since exposure to both drugs is likely to occur in the last two trimesters of human pregnancy, it is important to determine whether such exposure can have effects upon brain or behavior of offspring. Pregnant CD rat dams were given daily subcutaneous injections of saline, CLON, or LOF on days 8 through 20 of gestation. Maternal weight during gestation, neonatal weight and neurochemical measures were monitored. Maternal body weight was reduced in a dose dependent manner. At PND 1 brain ornithine decarboxylase (ODC) activity was reduced in LOF- but not CLON-exposed pups of both sexes. At this age no alteration was seen in whole brain catecholamine levels or in whole brain alpha-2-adrenergic binding.
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PMID:Neurochemical evaluation of rats prenatally exposed to the adrenergic agonists clonidine and lofexidine. 290 69

The cardiovascular structural remodelling associated with psychogenic hypertension was investigated in genetically normotensive rats subjected to isolation stress. Male Wistar rats were stressed by intermittent social isolation and compared to control rats living in groups. The stressed rats had higher systolic blood pressures than the control rats throughout the study. After 1 week of isolation, ornithine decarboxylase activity, a marker for hypertrophy, was increased in the right ventricle of the stressed rats. After 6 weeks of intermittent isolation, the myocardium of the stressed rats was hypertrophied, involving both right and left ventricles. The aorta was also hypertrophied, whereas the tail artery remained unaffected. Later, after 12 weeks of isolation, the left ventricular hypertrophy persisted whereas the right ventricle and aorta returned to normal. It seems, therefore, that social stress hypertension is accompanied by very early structural changes, which affect at least the heart and the aorta, and cannot be directly linked to the severity or duration of hypertension.
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PMID:Cardiovascular structural changes induced by isolation-stress hypertension in the rat. 324 Nov 86

Borderline hypertensive (BHR) rats are the first generation offspring of a cross of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. In adulthood, BHRs have systolic blood pressures in the 140-160 mm Hg range. If subjected to chronic stress paradigms, however, BHRs develop sustained and permanent elevations in systolic blood pressure (180-200 mm Hg). In the present study, we examined the functional development of cardiac and adrenal medullary responses to reflex activation of the sympathetic nervous system in preweanling BHR and WKY rats. Pups of the two groups were injected with insulin or saline at 4, 8, 12, or 16 days of age and sacrificed 3 h later. Insulin produces an acute lowering of blood glucose which is attended by a centrally mediated increase in sympathetic activity. The induction of ornithine decarboxylase (ODC) activity in heart and the depletion of epinephrine from the adrenal medulla were biochemical indicators of functional sympathetic neurotransmission. WKY and BHR pups had similar levels of cardiac ODC activity under basal conditions and following administration of insulin. In contrast, BHRs had higher amounts of adrenal norepinephrine and epinephrine from 4 to 16 days of age and greater depletion of adrenal epinephrine following insulin administration at 8, 12 and 16 days of age. These findings indicate that BHRs have a greater capacity for catecholamine biosynthesis, storage and release in the adrenal medulla during the preweanling period compared to age-matched normotensive WKY controls. This alteration in the adrenal medulla during the preweanling period may contribute to the susceptibility of adult BHR rats to stress-induced hypertension.
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PMID:Development of cardiac sympathetic and adrenal-medullary responses in borderline hypertensive rats. 332 89

Functional development of the sympathetic nervous system was examined in inbred Dahl salt-sensitive (S/JR) and salt-resistant (R/JR) rats by assessing cardiac and adrenal medullary responses to insulin-induced hypoglycemia at 2, 4, 8, 12, and 16 days of age. Heart ornithine decarboxylase (ODC) activity and adrenal catecholamine content were measured in pups of the two strains 3 hours after administration of either saline or insulin. The centrally mediated increase in sympathetic outflow caused by insulin-induced hypoglycemia was attended by induction of heart ODC activity and depletion of adrenal epinephrine (EPI). No significant differences were found overall between R/JR and S/JR strains with regard to either heart ODC activity or adrenal epinephrine. This was true for basal values obtained from saline-injected pups as well as for measures from insulin-injected pups. Functional innervation of the heart was present in pups of both strains as early as 2 days of age, while in the adrenal medulla a significant response to stimulation was not detected until 8 days of age. While the susceptibility for hypertension in the salt-sensitive animals may well be linked to increased sympathetic tone, the present findings indicate that S/JR rats do not have an accelerated development or a hyperresponsiveness of sympathetic input to either the heart or the adrenal medulla during the pre-weanling period.
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PMID:Sympathetic responses of the heart and adrenal medulla in developing Dahl hypertensive rats. 360 26

A standardized stenosis was induced by applying a silver clip around the left renal artery in male rats. This resulted in arterial hypertension within 10 days (as determined by increase in heart weight). Ornithine decarboxylase (ODC) activity was determined in the right (untouched) kidney, the left kidney, and the adrenal glands 1 day, 10 days, and 3 months after the operation. There was no difference in ODC activity in the right kidney of the operated animals when compared with matched controls. In the left kidney (with artery stenosis), ODC activity decreased to 40% after 1 day. A partial recovery was seen after 10 days (ODC activity 70% of normal), and after 3 months ODC activity had normalized. Removal of the clip 1 day prior to killing induced in the 3-month group a more than two-fold increase in ODC activity in the previously clipped kidney; ODC activity in the contralateral kidney was not affected. Only minor changes in ODC activity occurred in the adrenal glands following the operation. Contents of putrescine and spermidine were increased in the left (stenotic) kidney, and after clip removal, also in the right (untouched) kidney. Our observations thus indicate that alterations in renal blood flow are rapidly followed by changes in ODC activity. Contents of putrescine, spermidine and spermine seemed to a great extent to be independent of the ODC activity.
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PMID:Renal polyamine metabolism in rats with renovascular hypertension. 401 83

Mechanisms of vascular hypertrophy induced by hypertension were studied in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with those from normotensive Wistar-Kyoto (WKY) rats. Fetal calf serum-stimulated ornithine decarboxylase (ODC) activity of cultured smooth muscle cells was greater in SHR and SHRSP than in WKY. Beta- but not alpha-adrenergic agonist stimulated ODC activity acutely in cultured smooth muscle cells from WKY, and isoprenaline-induced activation was blocked by the beta-blocker, propranolol, and enhanced by the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. These results indicate that cultured vascular smooth muscle cells from SHR and SHRSP are more prone to increase the protein synthesis than those from WKY through the trophic induction of ODC activity and that the regulation of ODC activity by catecholamines is mediated through beta-agonistic effect in cultured smooth muscle cells.
Hypertension
PMID:Studies of hypertension-induced vascular hypertrophy in cultured smooth muscle cells from spontaneously hypertensive rats. 619 73


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