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

To assess the role of the sympathetic nervous system in the development of genetic hypertension, blood pressure (BP) was recorded in conscious adult Lyon hypertensive (LH) and normotensive (LN) rats that had received daily injections of saline or guanethidine at 1-13 wk of age. Guanethidine abolished the pressor response to tyramine, decreased plasma norepinephrine by greater than 70% and plasma 3,4-dihydroxyphenylglycol by approximately 90%, and did not change plasma epinephrine. Bilateral adrenalectomy further reduced plasma norepinephrine to 8 and 5% of control levels in LH and LN rats, respectively. BP was lowered (-7%) in sympathectomized rats, but the mean absolute BP difference between LH and LN rats was unaltered. Despite marked supersensitivity to alpha-adrenoreceptor stimulation, phentolamine induced only a small transient depressor response, which was abolished by adrenalectomy in sympathectomized rats. It is concluded that the sympathetic nervous system is not necessary for the development of hypertension in LH rats. After sympathectomy, circulating catecholamines, which mostly derive from the adrenal medulla, play only a minor role in BP maintenance.
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PMID:Blood pressure maintenance in hypertensive sympathectomized rats. I. Adrenal medullary catecholamines. 168 45

Ca sensitivity and sensitivity to diltiazem were studied in two strains of genetically hypertensive rat [spontaneously hypertensive rats (SHRs) and genetically hypertensive (GH) rats] and their normotensive control strains [Wistar-Kyoto (WKY) and normal Wistar (N) rats] at two ages before and after establishment of significant hypertension. Ca sensitivity was equal in both hypertensive/normotensive strain pairs from young rats but significant relative increases in Ca sensitivity were present in older rats. Sensitivity to the vasodilating action of diltiazem in vessels precontracted using K+ was also present in adult rats. These results suggest that the abnormality in Ca sensitivity seen in genetic hypertension in rats is an acquired characteristic not involved in the etiology of hypertension.
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PMID:Sensitivity to Ca2+ and the effects of a calcium channel antagonist in resistance vessels from two strains of genetically hypertensive rat. 170 10

Hypertension may result from vascular hypertrophy or hyperplasia due to enhanced growth of vascular smooth muscle cells (VSMCs), which has been demonstrated in VSMCs from spontaneously hypertensive rats (SHRs) compared to Wistar-Kyoto (WKY) rats. To determine whether this enhanced mitogenesis is peculiar to SHRs or a general phenomenon in genetic models of hypertension, we have measured indices of cell growth [3H]-thymidine uptake in VSMCs from SHRs and New Zealand genetically hypertensive (GH) rats and controls [WKY and normal Wistar (N) rats] cultured in fetal calf serum (FCS) or angiotensin II (Ang II, 0.1 microM) in either 3% heat-treated FCS or serum-free medium. SHR cell numbers increased faster in response to both mitogens compared to WKY rats. However, GH and N rat responses to FCS were the same. Ang II caused a significant but similar increase in cell numbers in both GH and N rat cells (i.e., Ang II caused hyperplasia in all four strains) but [3H]thymidine uptake was significantly greater in GH rat cells. Ang II increased the total well protein content but not protein normalized on cell number, i.e., no hypertrophic effect of Ang II was seen in these actively dividing cells. We conclude that (a) growth properties of VSMCs from rats with genetic hypertension vary between strains; the differences in growth may reflect strain-specific variation in the activity of intracellular signalling systems subserving mitogenesis; and (b) Ang II causes VSMC hyperplasia.
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PMID:Mitogenesis in cultured vascular smooth muscle cells from two rat models of hypertension in response to fetal calf serum and angiotensin II. 170 14

Environmental factors, genetic polymorphism and differences in experimental design have been the main impediments to evaluating the evidence for a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. The present paper reviews the results obtained in the Milan hypertensive rat (MHS) and in its corresponding normotensive strain (MNS) in order to illustrate our approach to defining the role of cation transport abnormality in a particular type of genetic hypertension. Kidney cross-transplantation between the strains showed that hypertension is transplanted along with the kidney. Proximal tubular cell volume and sodium content were lower in MHS rats while sodium transport across the brush border membrane vesicles of MHS rats was faster. Erythrocytes of MHS rats have a smaller volume, faster Na,K cotransport and a lower Km for internal sodium compared with MNS rats. The faster cotransport is also present in renal cells of the ascending limb and in vascular muscle cells. Moreover, these erythrocyte abnormalities are genetically associated in F2 hybrids and are primarily determined in the stem cells. These differences in ion transport between MHS and MNS rats are not present when studied in erythrocyte inside-out vesicles, which are deprived of membrane skeletal proteins, suggesting that a molecular abnormality underlies the functional one. We have identified a point mutation of one of these cytoskeletal membrane protein adducin genes in MHS rats. At present we are evaluating the possibility that mutation of the adducin gene in MHS rats might account for the differences in ion transport and, therefore, in blood pressure between the two strains.
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PMID:Genetic aspects of ion transport systems in hypertension. 171 Feb 65

The objective of this study was to test the hypothesis that the vasodilator prostaglandins E2 (PGE2) and PGI2) participate in the mechanisms involved in the increased renal vascular reactivity (RVR) observed in genetic hypertension. Studies were performed on anesthetized young and adult spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Renal blood flow (RBF) was measured during bolus injections into the renal artery of different doses of viprostol and iloprost (stable receptor agonists of PGE2 and PGI2, respectively) before and during inhibition of prostaglandin synthesis by indomethacin. Under control conditions, PGE2 increased RBF equally in young SHR and WKY. However, after cyclooxygenase inhibition the PGE2-induced increase in RBF was larger in young SHR than in WKY. Adult SHR displayed reduced reactivity to PGE2 relative to age-matched WKY under control conditions. This strain difference was abolished after indomethacin administration. PGI2 increased RBF slightly in young rats before and after indomethacin administration. In contrast, both strains of older animals displayed significant increases in RBF in response to PGI2 injections. Indomethacin administration enhanced this PGI2-induced relaxation in adult SHR but not WKY. We propose that the action of vasodilator PGs in the renal vasculature of rats developing hypertension may be limited by low density of their renal receptors and/or the opposing action of vasoconstrictor PGs. As age advances, PGI2 seems to be activated, possibly as part of a regulatory response to counterbalance the increased renal vascular resistance following the establishment of the disease.
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PMID:Renal vascular reactivity to vasodilator prostaglandins in genetically hypertensive rats. 173 88

Membrane microviscosity, phospholipid composition, and turnover were measured in cultured vascular smooth muscle cells isolated from mesenteric arteries of stroke-prone spontaneously hypertensive and age-matched, normotensive Wistar-Kyoto rats. Membrane microviscosity, measured with fluorescence polarization, revealed greater microviscosity (lower fluidity) of the membranes isolated from smooth muscle cells from hypertensive as compared with those isolated from normotensive rats (p less than 0.01). Preincubation of membranes from hypertensive rats with 5 mM calcium reduced membrane microviscosity in "core" and in "surface" regions of the bilayer toward values observed in Wistar-Kyoto rats. Phospholipid composition did not differ between intact aortas and cultured mesenteric cells or between those tissues obtained from normotensive and from hypertensive rats. The total lipid-associated radioactivity was significantly lower in cells from stroke-prone spontaneously hypertensive rats than in those from Wistar-Kyoto controls (p less than 0.01). Phosphatidylcholine incorporated 70% and phosphatidylinositol 16% of total lipid-associated radioactivity, with no difference between cells from hypertensive and normotensive animals. Turnover of phosphatidylethanolamine was greater in cells from Wistar-Kyoto rats (p = 0.02), whereas turnover of phosphatidylserine was greater in cells from stroke-prone spontaneously hypertensive rats (p = 0.04). The greater microviscosity of the lipid bilayer in hypertension is a generalized defect of the matrix in which the transport proteins function. We hypothesize that this defect is responsible for the multiple abnormalities of membrane transport systems that have been described in genetic hypertension.
Hypertension 1991 Dec
PMID:Lipid bilayer in genetic hypertension. 174 56

Evidence has been presented that: 1.) Changes in lipid bilayer alter the function of integral membrane proteins. 2.) There is less calcium bound to the plasma membrane in hypertension. 3.) Structural and functional abnormalities of the lipid bilayer have been reported in genetic hypertension. We hypothesize that multiple abnormalities of membrane transport systems in hypertension are secondary to an inherent abnormality of the lipid bilayer in which these transport proteins reside.
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PMID:Many membrane abnormalities in hypertension result from one primary defect. 180 3

Because of the known influence of the lipid bilayer on membrane transport systems, the characteristics of the bilayer from vascular smooth muscle and from platelets were studied in genetically hypertensive and in normotensive rats. Membrane microviscosity was measured by the degree of polarization of embedded fluorophores. Both the core of the bilayer in which diphenylhexatriene (DPH) was embedded and the surface in which the trimethyl-ammonium derivative of DPH (TMA-DPH) was embedded evidence a greater microviscosity (less fluid) in the hypertensive than in the normotensive rat. We had previously observed that monovalent cation fluxes were elevated in hypertension. We now observe that an increase in calcium concentration reverses both the elevated microviscosity and the increased cation fluxes. Conversely an increased incorporation of cholesterol in the membrane increases both the microviscosity and the cation fluxes. We hypothesize that the greater microviscosity of the lipid bilayer in hypertension constitutes a generalized defect of the matrix in which the transport proteins function. We further hypothesize that this defect is responsible for the multiple abnormalities of membrane transport systems and the increase in vascular reactivity that have been described in genetic hypertension.
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PMID:The primacy of membrane microviscosity in genetic hypertension. 181 55

Streptozotocin (STZ) treatment on neonatal rats produces a non-insulin-dependent diabetes mellitus (NIDDM) model in adulthood. Applying this model to spontaneously hypertensive rats (SHR), we designed the present study to develop a new model of NIDDM with genetic hypertension. Two-day-old male and female SHR were intraperitoneally injected with 25.0-75.0mg/kg STZ, and two-day-old Wistar Kyoto rats (WKY) of both sexes, which are a normotensive control strain for SHR, were similarly injected with 75.0-150.0mg/kg STZ. Control rats received vehicle alone. The relationships between the doses of the STZ injected and the changes of the metabolic variable and blood pressure were examined for 12 weeks following the treatment. Plasma glucose levels in male SHR increased in a dose-dependent manner at 12 weeks, control 122 +/- 8 (SEM) mg/dl, 25.0mg/kg STZ 139 +/- 13mg/dl (ns), 37.5mg/kg STZ 240 +/- 51mg/dl (ns), 50.0mg/kg STZ 359 +/- 39mg/dl (p less than 0.01), 62.5mg/kg STZ 419 +/- 33mg/dl (p less than 0.001) and 75.0mg/kg STZ 513 +/- 10mg/dl (p less than 0.001), whereas in male WKY, only mild hyperglycemia developed in case of the higher doses of STZ given, control 112 +/- 4mg/dl, 75.0mg/kg STZ 136 +/- 18mg/dl (ns), 100.0mg/kg STZ 204 +/- 40mg/dl (ns), 125.0mg/kg STZ 219 +/- 37mg/dl (p less than 0.05), and 150.0mg/kg STZ 177 +/- 12mg/dl (p less than 0.01). The development of hypertension was not affected by the neonatal STZ treatment in male SHR at 11 weeks, systolic blood pressure being control 210 +/- 7mmHg, 25.0mg/kg STZ 217 +/- 5mmHg (ns), 37.5mg/kg STZ 202 +/- 3mmHg (ns), 50.0mg/kg STZ 216 +/- 6mmHg (ns), 62.5mg/kg STZ 210 +/- 6mmHg (ns), and 75.0mg/kg STZ 209 +/- 5mmHg (ns). For the long-term observation, STZ-treated male SHR were divided into mild diabetes group (plasma glucose at 12 weeks less than 300mg/dl, mean 195 +/- 21mg/dl) and severe diabetes group (greater than or equal to 300mg/dl, mean 445 +/- 18mg/dl). Hyperglycemia in both groups was maintained until 28 weeks, plasma glucose being control 112 +/- 4mg/dl, mild diabetes group 161 +/- 10mg/dl (p less than 0.01), and severe diabetes group 419 +/- 25mg/dl (p less than 0.001) but it later gradually ameliorated, plasma glucose at 52 weeks being control 120 +/- 3mg/dl, mild diabetes group 131 +/- 7mg/dl (ns), and severe diabetes group 220 +/- 43mg/dl (ns). However, hypertension persisted in both diabetes groups until 52 weeks, systolic blood pressure being control 209 +/- 6mmHg, mild diabetes group 199 +/- 9mmHg (ns), and severe diabetes group 221 +/- 6mmHg (ns).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A new animal model of non-insulin-dependent diabetes mellitus with hypertension: neonatal streptozotocin treatment in spontaneously hypertensive rats. 183 97

Sodium has been identified as a causal factor in the development of hypertension in experimental animal models as well as in clinical human subjects. Sodium is also known to play a role in modulating myocardial mass and its pattern of myosin isozyme distribution. In the rodent model, the accumulation of V3 myosin isozyme (MI), due to the modulating influence of sodium, has been shown to be associated with persistent cardiac hypertrophy and heart failure. In this paper, we have examined the effect of the restriction of dietary sodium on blood pressure, ventricular weight and myosin isoforms in spontaneously hypertensive rats (SHR) and the relationship of these parameters with age. In 10- to 11-week-old SHR, dietary sodium restriction for 14 weeks resulted in a significant reduction in ventricular mass associated with systolic shifting of myosin isoform from V3 type to V1 type with no change in systolic blood pressure level; dietary sodium restriction also showed a significant reduction in body weight. When the effect of dietary sodium restriction (for 8 weeks) was studied in relation to age (in 11-, 16- and 24-week-old rats) a significant shift in myosin isoform from the V3 to the V1 type was noted in the 11-week-old rats; a slight but significant shift was noted in 16-week-old rats, and no change in myosin isoform distribution was noted in the 24-week-old SHR. The alteration in myosin isoform and myocardial mass in the 11- and 16-week-old rats was independent of changes in systolic blood pressure. This study demonstrates that sodium plays an important role not only in modulating myocardial mass but also in changing the biochemical composition of the heart. This study also suggests that in genetic hypertension, the restriction of sodium at a very young age may fully prevent the development of hypertension and hypertrophy. However, the mechanism by which the sodium ion modulates myocardial mass and the expression of either V1 or V3 myosin genes is unknown; the question of how sodium affects the cardiac function also remains. Some evidence suggests that sympathetic outflow may play an important role, but further studies are needed to validate this.
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PMID:Effect of sodium deprivation on cardiac hypertrophy in spontaneously hypertensive rats: influence of aging. 183 55


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