ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A review is presented of the potential ways in which insulin resistance and hypertension may be linked. Although controversy exists as to the role insulin resistance and hyperinsulinemia play in the pathogenesis of hypertension, data are presented from both obese and nonobese subjects that strongly suggests that selective insulin resistance and hypertension are directly related. Because insulin resistance may be both tissue and pathway specific, it is possible that the degree to which insulin resistance is tissue specific determines whether hypertension will develop in specific individuals or animals.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Infusion of endothelin has been observed to increase hematocrit, and the peptide also stimulates release of atrial natriuretic peptide (ANP) both in vitro and in vivo. We studied the relation of these two actions of endothelin in anesthetized, bilaterally nephrectomized Sprague- Dawley rats. Infusion of endothelin (25 ng/kg/min) for 45 minutes produced a modest increase in blood pressure of 12% from a baseline of 99 ±5 mm Hg and an increase in hematocrit of 8.0±0.6%, reflecting a reduction in plasma volume of 13.1 ±0.9%. These changes each exceeded greatly those observed after 45 minutes of vehicle infusion. Plasma protein concentration, however, increased only by 4.2 ±0.6%, suggesting protein extravasation, which was confirmed by finding an endothelin-dependent increase in the accumulation of Evans blue dye in heart, skeletal muscle, and intestine, but not liver, lung, brain, or testis. Endothelin infusion increased plasma immunoreactive ANP concentration from 196±50 to 722±203 pg/ml (p<0.02), and a close correlation existed between the increase in plasma immunoreactive ANP and immunoreactive endothelin concentrations as a result of the infusion (r=0.84,p<0.01). Pretreatment of rats with rabbit anti-rat ANP antiserum did not affect baseline variables but led to an exaggerated increase in blood pressure (25.3±2.9%,p<0.002 versus endothelin alone). No change in hematocrit occurred. Thus, the increase in plasma immunoreactive ANP concentration resulting from endothelin infusion mediates the increase in hematocrit through an increase in vascular permeability to whole plasma. The exaggerated pressor effect of the infused endothelin in the presence of ANP antiserum suggests that ANP may modulate the vasoconstrictor actions of endothelin in vivo.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The effects of an increase in intraluminal pressure and flow on the diameter and active smooth muscle tone of pial arteries was studied in perfused segments. Resistance arteries (approximately 250-300 /μm i.d.) were perfused under controlled pressure and flow conditions, and changes in arterial diameter registered with an automated video device. In any particular segment, diameter measurements were normalized to that observed at 5 mm Hg. Changes in active wall force were determined by relating the observed diameter under a particular set of conditions to the diameter at the same intramural pressure when smooth muscle tone was inhibited (calcium-free physiological saline solution) and to the diameter when smooth muscle cells were activated close to maximum (KC1; 89 mM). At 60 mm Hg, the diameter decrease of 21% in the absence of flow represented stretch-induced tone. No additional changes in diameter were encountered with a flow of 20 μl/min. Diameter decreased a further 7% at 100 /nl/min. When intraluminal pressure was 90 mm Hg, diameter decreased 39% without flow. Additional constriction of 10% and 19% occurred at flows of 20 and 100 μl\Jmin, respectively. At the higher pressure, the vasoconstriction occasioned by flow was significantly greater than that at the lower pressure. After endothelium inactivation by passing hypo-osmotic Krebs' solution followed by air through the segment, mean diameter was less at each combination of pressure and flow, although this difference did not reach statistical significance. The diameter reductions to increases in pressure from 60 to 90 mm Hg and to flow at 40 μl/min were not altered by endothelium inactivation. We conclude that the vasoconstrictor effects of flow as well as pressure are augmented at high intravascular pressures and that these constrictor effects are independent of the endothelium.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Dose-response curves to topically applied acetylcholine, bradykinin, and nitroprusside were obtained by intravital microscopy in arcading arterioles of the spinotrapezius muscle of control (n=9) and one-kidney, one clip hypertensive (1K1C) rats (n=ll) of 4 weeks' duration before and during superfusion with the specific inhibitor of nitric oxide formation NG-monomethyl L-arginine (LNMMA) (10-4M) and both LNMMA (10-4M) and indomethacin (2.8 xlO"5 M). Resting arteriolar tone was higher in 1K1C rats than in controls, and vasodilation to acetylcholine and bradykinin, but not to nitroprusside, was reduced (p<0.05) in 1K1C rats compared with controls. LNMMA increased arteriolar tone (p<0.05) and inhibited the vasodilator responses to acetylcholine and bradykinin (p<0.05) in controls but not in 1K1C rats. LNMMA did not alter the response to nitroprusside in either group. Addition of indomethacin to LNMMA increased arteriolar tone and markedly reduced the response to bradykinin, but not to acetylcholine or nitroprusside, in both groups. These findings suggest that resting arteriolar tone is increased in 1K1C rats partially because of the decreased basal release or synthesis of nitric oxide. Responses to the endothelium-dependent vasodilators acetylcholine and bradykinin were attenuated in 1K1C rats, possibly because of changes in synthesis or release of nitric oxide for acetylcholine and of prostacyclin for bradykinin, because the response to the endothelium-independent vasodilator nitroprusside did not differ between the groups.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The aim of the present study was to examine the involvement of the sympathetic nervous system in the generation or release of vascular nitric oxide. In urethane-anesthetized rats, the administration of the novel nitric oxide synthesis inhibitor L-jV-nitro arginine (LNA) (0.02 mmol/kg i.v.) increased mean arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The intravenous administration of L-arginine (60 nig/kg plus 12 mg/kg/ min i.v.) produced small reductions in arterial pressure and vascular resistances and abolished the hemodynamic effects of LNA. Pretreatment with the ganglion blocking agent chlorisondamine lowered mean arterial pressure and vascular resistances, abolished the LNA-induced pressor and renal vasoconstrictor response, and attenuated the increases in mesenteric and hindquarter resistances. In contrast, the vasodilator hydralazine lowered mean arterial pressure and vascular resistances to levels equivalent to that of ganglionic blockade; however, the subsequent administration of LNA still produced significant increases in arterial pressure and regional vascular resistances. In ganglion-blocked rats in which pressure and vascular resistances were returned to normal levels by infusion of arginine vasopressin or phenylephrine, the pressor and vasoconstrictor effects of LNA were restored. However, phenylephrine was significantly more efficacious and markedly exaggerated the action of LNA. These results suggest that the sympathetic nervous system plays an important role in modulating the synthesis or release of vascular nitric oxide through the effects of 1) normal sympathetic discharge, 2) humoral activation of α-adrenergic receptors, and 3) vascular tone per se.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Hypertension-associated growth of vascular smooth muscle cells might be mediated in vivo by platelet-derived growth factor (PDGF). Our previous investigations in hypertensive rats failed to demonstrate changes in aortic steady-state mRNA levels of PDGF A or B chains. The current studies were performed to determine whether hypertension might affect the expression of PDGF receptors. We studied PDGF α and βreceptor gene expression by Northern analysis using human and rat cDNA probes. Studies of tissue distribution revealed that PDGF β-receptor mRNA was most abundant in total aorta and aortic media, whereas the PDGF α-receptor mRNA was most abundant in the lung and was expressed at low levels in aortic tissue. Deoxycorticosterone acetate (DOCA)-salt hypertension induced a threefold increase in aortic steady-state PDGF β-receptor mRNA levels. Aortic PDGF /J-receptor expression also was higher in spontaneously hypertensive rats (SHRs) when compared with age-matched normotensive Wistar-Kyoto (WKY) controls. Aortic PDGF α-receptor steady-state mRNA levels were unchanged in DOCAsalt hypertension and were expressed at similar levels in WKY rats and SHRs. Unlike the findings with aorta, cardiac PDGF β- and α-receptor and PDGF B-chain expressions were unchanged in the DOCA-salt model and were decreased in SHRs. These findings indicate that hypertension can increase aortic steady-state mRNA levels for PDGF β-receptor. They also indicate that tissuespecific expression of the genes of the PDGF ligand/receptor system are differentially regulated in hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Previous studies demonstrated that in addition to an increased response to growth factors, cultured vascular smooth muscle cells derived from spontaneously hypertensive rats (SHRs) grow to a greater density than cells from normotensive Wistar-Kyoto (WKY) rats. Transforming growth factor β1, (TGF-β1,) has a bimodal effect on vascular smooth muscle cell growth, depending on cell density. The present study investigated the relation between cell density and expression of the proto-oncogene c-fos and TGF-β1, in cells from WKY rats and SHRs. The results demonstrate an increased accumulation of c-fos mRNA in calf serum-stimulated SHR cells but only at a high cell density. The expression of TGF-β1mRNA was enhanced in growing SHR cells at every density studied as early as 24 hours after inoculation, with a further increase at later times. The effect of exogenous TGF-β1on new DNA synthesis was evaluated by [3H]thymidine incorporation. At a low cell density, TGF-β1, had no effect on DNA synthesis in either WKY or SHR vascular smooth muscle cells. At a high cell density, there was a significant increase of DNA synthesis in response to TGF-β1, in SHR cells without any effect in WKY cells. In conclusion, contact inhibition of vascular smooth muscle cells from SHRs at a higher cell density is accompanied by an earlier expression of the marker gene c-fos and preceded by an exaggerated expression of TGF-β1,. Considered together with the stimulating effect of exogenous TGF-β1] at a high cell density, the results suggest an abnormal feedback control (autocrine stimulation) of this growth factor and its involvement in altered contact inhibition of vascular smooth muscle cells from SHRs.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Loss of microvessels (anatomic rarefaction) occurs in chronic reduced renal mass (RRM) hypertension and is mediated via structural degeneration of vascular smooth muscle (VSM) and endothelial cells. The purpose of the present study was to determine if structural changes occur in VSM cells of the microvessels that remain in the tissue of rats with chronic RRM hypertension. Samples of cremaster muscles were taken from normotensive control rats and rats with acute (3-7 days) and chronic (14-28 days) RRM hypertension (75% reduction in kidney mass with 4% NaCl loading). The samples were fixed in situ and processed for light and electron microscopy. Ultrastnictural morphology of VSM cells in terminal artenoles of control animals was normal. Although VSM morphology in many microvessels of RRM hypertensive rats was also normal, some vessels exhibited structural changes that were not present in artenoles of the normotensive animals. The most striking change was the appearance of more extensive dense bodies anchoring the contractile filaments around the outer membrane of the cells. Extreme vasoconstriction was observed in some artenoles of RRM rats as long as 2 weeks after salt loading. Focal areas of VSM cell proliferation were evident Many of the changes occurring in RRM were detected as early as 1 week after the onset of hypertension. These observations suggest that renal mass reduction-salt loading hypertension is associated with early structural and functional changes in the VSM cells.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID