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Biomedical subjects

C A Hamilton

Publications and source records attributed to C A Hamilton.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effects of nitric oxide and superoxide on relaxation in human artery and vein.

Endothelium-derived relaxing and contracting factors play an important role in atherosclerosis, re-stenosis and graft survival. Internal thoracic artery (ITA) and saphenous vein (SV) are used as conduit vessels in coronary artery bypass graft surgery (CABG). The long-term graft patency rate is higher with ITA than SV. Effects of nitric oxide and superoxide on vascular relaxation in isolated rings of ITA and SV from patients undergoing CABG were investigated. NG-nitro-L-Argenine methylester (L-NAME) was used to block nitric oxide synthesis and superoxide dismutase (SOD) and tiron to scavenge superoxide. Responses to carbachol were taken as a measure of stimulated nitric oxide release and increased responses to phenylephrine after addition of L-NAME as a measure of basal nitric oxide release. Immunocytochemical demonstration of endothelial nitric oxide synthase was performed using anti-endothelial nitric oxide synthetase (anti-eNOS) NOS antibody. Stimulated nitric oxide release was observed in ITA and SV but basal release was reduced or absent in SV. Treatment with SOD and tiron potentiated carbachol stimulated relaxation in ITA and SV. Tiron treatment resulted in a significant increase in basal nitric oxide in veins. eNOS immunoreactivity was more intense in ITA than SV, compatible with reduced nitric oxide production in veins. This may contribute to the reduced patency of venous grafts.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1997

Low-density lipoprotein and oxidised low-density lipoprotein: their role in the development of atherosclerosis.

Oxidation of low-density lipoprotein (LDL) may be implicated in the development of atherosclerotic disease. Oxidised LDL is taken up more readily by monocyte-derived macrophages than LDL. Antibodies to oxidised LDL are found in atherosclerotic lesions, Increased risk of ischaemic heart disease is associated with a preponderance of small dense LDL particles, which are more susceptible to oxidation. Proatherogenic alterations in cell biochemistry and signalling pathways occur in the presence of LDL and more markedly oxidised LDL. In vitro antioxidants inhibit changes in cell biochemistry, while in vivo, they have been shown to attenuate or reverse development of atherosclerosis.

Antioxidants↗
PubMed1997

Sex differences in the abundance of endothelial nitric oxide in a model of genetic hypertension.

A deficiency of nitric oxide may be responsible for the increased vascular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal females are relatively protected from hypertension and cardiovascular complications. Levels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) and that superoxide may be responsible for at least some of these differences. We studied vascular reactivity in endothelium-intact aortic rings from WKY and SHRSP. We measured nitric oxide synthase activity in endothelial cells removed from aortas and also measured circulating nitrite/nitrate levels. We found the response to N(G)-nitro-L-arginine methyl ester to be significantly greater in WKY compared with SHRSP (95% CI: 20 to 174; P=.015) and in females compared with males in WKY (95% CI: 143 to 333; P=.00004) and SHRSP (95% CI: 70 to 224; P=.0006). Endothelial nitric oxide synthase activity was significantly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P=.016). The EC50 for relaxation to carbachol was significantly greater in male rats compared with female rats (95% CI: -1.1 to -0.2; P=.003) within the SHRSP strain. The maximum relaxation to carbachol was significantly attenuated in stroke prone spontaneously hypertensive compared with Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P=.015). Diethyldithiocarbamate had a significantly greater effect on the stroke prone spontaneously hypertensive rats' carbachol response than that of Wistar-Kyoto rats (95% CI: 14.3 to 47.0; P=.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nitric oxide availability may be responsible for sex differences independently of endothelial nitric oxide synthase activity and superoxide.

Animals↗
PubMed1996

Femoral artery occlusion following pelvic cancer surgery.

Acute arterial occlusion in the lower extremities of patients with gynecologic cancers may not be immediately recognized in the postoperative period, despite the known risk of hypercoagulability associated with malignancy. Such delays in recognition and treatment can result in irreversible but potentially preventable tissue injury. This report describes three cases of acute arterial occlusion of the femoral and/or external iliac arteries in the immediate postoperative period following radical pelvic surgery. Two patients lost the involved limb due to irreversible changes resulting from prolonged ischemia. One patient was diagnosed while the involved limb was still viable and surgical revascularization was successfully performed. These cases illustrate the potential morbidity in unrecognized acute limb ischemia and the case with which it may be overlooked. Systematic documentation of arterial patency is recommended in the postoperative period, noting peripheral pulses and patient complaints related to the lower extremities. Rapid diagnosis and surgical intervention significantly increase the chance of maintaining viability of the involved limb.

Adult↗
PubMed1996

Effects of manipulation of dietary cholesterol on the function of the thoracic aorta from New Zealand white rabbits.

Animal studies, while generally showing loss of endothelium-dependent responses after an elevation in plasma cholesterol, have provided conflicting reports with regard to recovery of function after normalisation of cholesterol level. Therefore, we assessed changes in vascular function after a period of hypercholesterolaemia and the subsequent effect of normalisation of cholesterol levels. Contractile responses to phenylephrine (PE) and endothelium-dependent relaxation in response to carbachol were examined in thoracic aorta from New Zealand White rabbits (NZW) fed a 0.3% cholesterol diet for 20 weeks, from NZW fed a 0.3% cholesterol diet for 20 weeks, followed by standard diet for 20 more weeks, and from their respective age-matched controls. Cholesterol levels were increased in rabbits receiving the 0.3% cholesterol diet (12.7 +/- 3.2 mM; 0.5 +/- 0.1 mM control) and returned to normal when standard diet was reintroduced (0.8 +/- 2.0 mM). Contractile responses were not affected by the period of hypercholesterolaemia. Carbachol-induced relaxation of a submaximal PE contraction was impaired after the period of hypercholesterolaemia (Emax 69 +/- 9%; 95 +/- 3% age-matched (control); the effect was reversed after reintroduction of standard diet (Emax 79 +/- 6%; 82 +/- 2% age-matched control). Our results demonstrate that endothelium-dependent relaxation is impaired after a long-term 0.3% cholesterol diet. Furthermore, after reintroduction of a normal diet, there is no further impairment of endothelium-dependent relaxation and endothelium function improves.

Adrenergic alpha-Agonists↗
PubMed1996

Magnetization transfer or spin-lock? An investigation of off-resonance saturation pulse imaging with varying frequency offsets.

PURPOSE: To characterize near-resonance saturation pulse MR imaging on a 1.5-T scanner in order to gain insight into underlying mechanisms that alter tissue contrast and to optimize the technique for neuroimaging. METHODS: Off-resonance saturation pulses were applied to T1-weighted, spin-density-weighted, and T2-weighted sequences at frequency offsets ranging from 50 Hz to 20,000 Hz down field from water resonance. Suppression ratios were determined at each offset for phantom materials (MnCl2 solution, gadopentetate dimeglumine, corn oil, water, and agar), normal brain structures, and a variety of brain lesions. RESULTS: Signal suppression of MnCl2 on T1-weighted images occurred at offsets of less than 2000 Hz even though no macromolecules were present in the solution. Only those phantom materials and tissues with short or intermediate T1 relaxation times and relatively large T1/T2 ratios were sensitive to changing frequency offsets. Suppression of brain increased from approximately 20% at 2000 Hz offset to approximately 45% when the offset was reduced to 300 Hz. In human subjects, the net effect of reducing the frequency offset was to increase T2 contrast on T1-weighted, spin-density-weighted, and T2-weighted images. Distilled water and contrast material did not suppress except at very low offsets ( < 300 Hz). A frequency offset of 300 Hz was optimal for maximizing conspicuity between most contrast-enhancing lesions and adjacent brain while preserving anatomic detail. CONCLUSION: Suppression of MnCl2 indicates that magnetization transfer is not the sole mechanism of contrast in near-resonance saturation MR imaging. Spin-lock excitation can reasonably explain the behavior of the phantom solutions and the increase in T2 contrast of tissues achieved as the frequency offset is decreased from 2000 Hz to 300 Hz. Below 300 Hz, saturation is presumably caused by spin-tip effects. With our pulse design, an offset of 300 Hz is optimal for many routine clinical imaging examinations.

Adult↗
PubMed1995

Imidazoline receptors, subclassification, and drug-induced regulation.

Overall, as summarized in TABLE 6, a variety of responses to chronic drug treatment were observed depending on the drug, the tissue, and the ligand. Taken together these studies support the concept that the three ligands bind to distinct sites. In addition, they suggest that idazoxan and possibly yohimbine act as agonists at the I2 site in kidney. Finally, the lack of regulation of the I1 site in hindbrain is consistent with the low incidence of withdrawal symptoms reported with imidazoline-preferring drugs.

Animals↗
PubMed1995

Near-resonance spin-lock contrast.

Spin-lock and spin-tip excitations are the two magnetization components created by the preparatory RF pulse of an MRI contrast enhancement sequence. Only spin-lock is inherently adiabatic, preserving spin alignment so that tissue-specific relaxation can generate desired saturation contrasts. Spin-tip is the rotating-frame oscillating excitation, and generally causes nonadiabatic loss of all detectable magnetization. Relative levels of spin-lock and spin-tip are important to understand as a function of the preparatory B1 delta amplitude, resonance frequency offset, delta, and the pulse waveform. These MR responses can be accurately analyzed theoretically and numerically by using Torrey's tipped coordinates to formulate Bloch's equations. At near-resonance offsets, (delta/gamma B1) less than 2.0, spin-lock contrast (SLC) depends strongly on T2, due to the nature of spin-lock T1 rho relaxation in the RF pulse interval. The relaxation rates 1/T1 rho and 1/T2 rho apply for active B1 delta, but remain linear combinations of ordinary (1/T1) and 1/T2) for motionally narrowed MR. The SLC increases rapidly as delta decreases below 2000 Hz; carefully chosen B1 delta rise times avoid spin-tip losses down to 150 Hz or less. The SL saturation enhances or multiplies any other indirect saturation effects that may be also present, such as magnetization transfer. A strong near-resonance SLC multiplier is advantageous for clinically practical MRI sequences that use short B1 delta pulses and fast SE multislice scan modes. Simulations based upon spin-lock/spin-tip theory and measured (T1,T2) yield excellent agreement with real MRI results for clinically practical fast multislice scans.

Computer Simulation↗
PubMed1995

Regulated expression of a contractile protein gene correlates with recovery of contractile function after reversible metabolic inhibition in cultured myocytes.

Little is known of the relation between recovery of contraction and the regulation of contractile protein gene expression in ventricular myocytes after severe ATP depletion. We have examined alterations in activation of an MLC-2 luciferase fusion gene in cultured neonatal rat ventricular myocytes produced by exposure to 2 mM Na CN and 20 mM 2-deoxyglucose, and after recovery is serum or serum free medium. The effects of metabolic inhibition followed by recovery on expression on an RSV-luciferase activity were also investigated. Myocytes were co-transfected with a CMV beta-galactosidase fusion gene, and luciferase activities were normalized relative to beta-galactosidase activity to control for transfection efficiency. Two hours of metabolic inhibition produced significant cell injury, as documented by disorganization of myofilaments, and reduction in luciferase and beta-galactosidase activity within transfected cells. Cells allowed to recover for 48 h in serum free hormone supplemented medium showed a further decline in corrected luciferase activity, consistent with a marked reduction in MLC-2 gene transcription. Cells recovered from severe metabolic inhibition in serum free medium also showed failure to redevelop contractile activity, and failure of redevelopment of organized myofibrils. In contrast, myocytes exposed to serum during the 48 h recovery period had a marked increase in luciferase activity, resumed contractile activity and re-established organized myofilaments. There were no significant differences between RSV luciferase activities in cells recovered in serum versus serum free media. In ventricular myocytes in which contraction was inhibited by exposure to 10 microM verapamil, MLC-2 luciferase activity declined by 87%. However, even when contractile activity was inhibited by exposure to verapamil during recovery from metabolic inhibition, exposure to serum containing medium caused a significantly greater increase in MLC-2 luciferase activity than did serum free medium. Thus, the effects of serum on MLC-2 gene expression were not solely due to an effect of serum on recovery of contractile activity. Verapamil had no consistent effect on expression of RSV luciferase. These results suggest that expression of the MLC-2 gene is markedly reduced following recovery from severe metabolic inhibition, an effect largely due to cessation of myocyte contractile activity. Resupply of growth factors present in fetal calf serum reactivate expression of this gene, and this is associated with resumption of contractile activity and redevelopment of organized myofibrils. These results suggest that reactivation of contractile protein gene expression during recovery from metabolic inhibition may be beneficial in allowing cells to recover from this insult.

Analysis of Variance↗
PubMed1995

Inducible L-arginine/nitric oxide pathway in human internal mammary artery and saphenous vein.

To characterize the L-arginine/nitric oxide (NO) pathway in human vascular smooth muscle (VSM), contractile responses of isolated internal mammary arteries (IMA) and saphenous veins (SV) were observed after induction of NO synthase by interleukin-1 beta (IL-1 beta) or by lipopolysaccharide (LPS). In IL-1 beta-treated endothelium-denuded rings, contractile responses to phenylephrine were reduced in SV rings only. Maximum phenylephrine-induced contraction was depressed by approximately 50%. This was not modified by the presence of indomethacin, NG-nitro-L-arginine methyl ester (L-NAME), or methylene blue (MeB). In LPS-treated vessels, contractile responses were depressed in both SV and IMA rings (40%), and this was not affected by indomethacin. In SV, L-NAME, NG-monomethyl-L-arginine, or MeB did not affect the inhibitory effect of LPS, whereas the effect was reversed in IMA by these inhibitors. In LPS-treated IMA, but not in SV, exogenous L-arginine evoked significant vasodilation (20%). We conclude that VSM of the human IMA possesses an L-arginine/NO pathway inducible by LPS. In SV, LPS or IL-1 beta treatment inhibits contraction by an unidentified system that is not dependent on NO synthase or on guanylate cyclase activities.

Aged↗
PubMed1995

Development and progression of atherosclerosis in aorta from heterozygous and homozygous WHHL rabbits. Effects of simvastatin treatment.

This study was conducted to define progression of atherosclerosis in both homozygous and heterozygous Watanabe heritable hyperlipidemic (WHHL) rabbits and to investigate the ability of the HMG CoA reductase inhibitor simvastatin to attenuate progression of the disease. We examined contractile responses to phenylephrine and endothelium-dependent relaxation in response to carbachol in thoracic aorta at 3, 6, 9, and 12 months in control New Zealand White (NZW) rabbits, homozygous WHHL rabbits, and heterozygous WHHL rabbits. Homozygous and heterozygous rabbits were treated with simvastatin (10 mg/kg per day) from 3 to 6 months and from 9 to 12 months of age. Simvastatin significantly reduced serum cholesterol levels in young heterozygotes, with a nonsignificant trend toward a reduction in older heterozygotes. In homozygotes, no significant fall was observed. Contractile function declined progressively with age in all groups--most in homozygotes and least in NZW rabbits. Relaxation was unaffected by age in NZW rabbits; relaxation declined in the heterozygotes and declined to a greater extent in homozygotes. Simvastatin retarded the loss of function in the young heterozygotes. Similar trends were observed in young homozygotes and older heterozygotes, with no effect in older homozygotes. Histological studies revealed the progressive development of early atherosclerosis in heterozygotes, and more advanced atherosclerosis was observed in homozygotes. Simvastatin did not inhibit development of atheroma. A correlation was observed between vascular function and structure. However, functional changes preceded the development of atheroma. In addition, we have demonstrated that simvastatin can help to reduce the loss of vascular function associated with the progression of atherosclerosis in the heterozygous WHHL rabbit.

Age Factors↗
PubMed1995

Role of superoxide in the depressed nitric oxide production by the endothelium of genetically hypertensive rats.

We undertook these studies to determine whether a deficient nitric oxide production in genetically hypertensive rats could result from its being scavenged by an excess production of superoxide. In one study we used a porphyrinic microsensor to measure nitric oxide concentrations released by cultured endothelial cells from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). SHRSP cells released only about one third the concentration of nitric oxide as did WKY cells. Treatment of cells with superoxide dismutase increased nitric oxide release, demonstrating that normally nitric oxide is scavenged by endogenous superoxide. The increase in nitric oxide release in response to superoxide dismutase treatment was more than twice as great from SHRSP as from WKY cells, demonstrating the greater amount of superoxide in the hypertensive rats. A direct measure of superoxide with the use of lucigenin demonstrated the presence of 68.1 +/- 7.1 and 27.4 +/- 3.5 nmol/L of this anion in SHRSP and WKY endothelial cells, respectively. The presence of superoxide in the rat aorta was also estimated by quantification of its effect on carbachol relaxation. This relaxation was diminished when endogenous superoxide dismutase was blocked by diethyldithiocarbamic acid. This blockade reduced the relaxation by 51.2 +/- 5.2% in SHRSP aortas and by only 22.0 +/- 8.2% (P = .015) in WKY aortas. Data from these diverse systems are in agreement that superoxide production is excessive in SHRSP tissues. This excess superoxide, by scavenging endothelial nitric oxide, could contribute to the increased vascular smooth muscle contraction and hence to the elevated total peripheral resistance of these rats.

Animals↗
PubMed1995

Emergency physicians. Accuracy in the diagnosis of stroke.

BACKGROUND AND PURPOSE: The role of emergency physicians in trials of acute stroke therapy is expanding. We investigated the ability of emergency physicians to accurately identify patients with stroke. METHODS: We reviewed all 446 patients who were evaluated in the emergency department and had an inpatient admitting or discharge diagnosis of ischemic or hemorrhagic stroke from May 1, 1992, to June 30, 1993. The final admitting diagnosis made by the emergency physician was compared with the final hospital discharge diagnosis, 95% of which were made by neurologists or neurosurgeons. RESULTS: All 76 patients with a final discharge diagnosis of intracerebral or subarachnoid hemorrhage were correctly diagnosed by the emergency physicians (sensitivity, 100%; positive predictive value, 100%). Of the 351 patients with a final discharge diagnosis of ischemic stroke or transient ischemic attack, 346 were correctly identified by the emergency physicians (sensitivity, 98.6%; positive predictive value, 94.8%). Nineteen patients were diagnosed with stroke or transient ischemic attack by the emergency physician but had a final discharge diagnosis other than stroke. Discharge diagnoses included paresthesia or numbness of unknown causes (3), seizure (2), complicated migraine (2), peripheral neuropathy (2), cranial nerve neuropathy (2), psychogenic paralysis (1), and other (7). CONCLUSIONS: Emergency physicians at a large urban teaching hospital with a comprehensive stroke intervention program can accurately identify patients with stroke, particularly hemorrhagic stroke. If similar accuracy can be documented in other types of hospitals, emergency physicians may become key providers of urgent stroke intervention.

Adult↗
PubMed1995

Combined effects of magnetization transfer and gadolinium in cranial MR imaging and MR angiography.

Magnetization transfer (MT) imaging is an MR technique in which image contrast is altered by applying RF pulses that saturate a restricted pool of hydrogen protons associated with cell membranes, proteins, and other macromolecules. Protons in this restricted pool, unlike those in tissue-free water, are not visible on MR due to their short T2 relaxation times. However, these restricted protons modulate the observed signal from free water by dipolar and chemical exchange interactions. In MT imaging, specifically tailored RF pulses are applied to saturate selectively the restricted macromolecular pool. This saturation is "transferred" to the free protons, causing their signal amplitude to decrease [1]. Increased signal intensity due to T1 shortening caused by gadolinium administration does not depend upon macromolecular interactions and is not appreciably suppressed by MT pulses (Fig. 1). Consequently, MT pulses act synergistically with gadolinium to increase the visibility of enhancing lesions by preferentially suppressing nonenhancing background tissue [2]. The purpose of this paper is to demonstrate the principles underlying the synergistic effects of MT saturation and paramagnetic contrast agents and to illustrate these effects in clinical MR imaging and MR angiography.

Brain↗
PubMed1995

Pertussis toxin sensitive endothelin-1 coupling to inositol phosphate formation via a GTP-binding protein: comparison in SHR and WKY cultured aortic smooth muscle cells.

The effects of pertussis toxin on endothelin-1 and noradrenaline coupling to inositol phosphate (IP) formation was investigated in cultured aortic smooth muscle cells from 14 week SHR and WKY rats. Endothelin-1 (10(-6) M) stimulated IP formation was decreased in cells from SHR compared to WKY (WKY 1117 +/- 157, SHR 668 +/- 85% of basal). Pre-incubation with pertussis toxin produced a significant and similar reduction in endothelin stimulated IP production in both SHR (54% reduction) and WKY (55%). However, the observed reduction in endothelin-1 stimulated IP accumulation was still apparent in SHR when compared to WKY. Pertussis toxin preincubation followed by removal of extracellular calcium reduced further the endothelin responses by similar amounts in SHR and WKY cells, but SHR stimulated IP formation remained significantly decreased compared to WKY. The extent of pertussis toxin ADP-ribosylation of Gi alpha was similar in both SHR and WKY cells. Endothelin-1 produced a reduction in the extent of ADP-ribosylation of Gi alpha and this was of similar magnitude in both SHR and WKY cell membranes. In contrast, noradrenaline stimulated IP formation was unaffected by pertussis toxin pre-incubation. It was concluded that SHR cells do not appear to have an alteration in endothelin-1 activated, pertussis toxin sensitive G-protein coupling to IP formation or in the dependence of inositol phosphate formation on extracellular calcium.

Animals↗
PubMed1995

The effects of perindopril on vascular smooth muscle polyploidy in stroke-prone spontaneously hypertensive rats.

OBJECTIVE: To quantify vascular smooth muscle polyploidy and growth kinetics in aortic cells from stroke-prone spontaneously hypertensive rats (SHRSP) and from normotensive Wistar-Kyoto (WKY) rats, and to examine the effects of treatment with the angiotensin converting enzyme (ACE) inhibitor perindopril on these parameters. DESIGN: The following experimental groups were used: young (age < 20 weeks) and old (age > 20 weeks) untreated WKY rats and untreated SHRSP; SHRSP treated with perindopril, and age- and sex-matched control SHRSP; and SHRSP treated with hydralazine and hydrochlorothiazide and age- and sex-matched control SHRSP. The effects of treatment of the SHRSP with perindopril for 30 days on vascular smooth muscle polyploidy and growth kinetics were measured and compared with the effects of equivalent antihypertensive doses of hydralazine and hydrochlorothiazide. METHODS: Vascular smooth muscle polyploidy was measured using flow-cytometry DNA analysis of freshly harvested cells. Growth curves were performed on cultured aortic cells. Plasma renin activity was measured by an antibody-trapping method, plasma angiotensin II (Ang II) by radioimmunoassay and plasma ACE activity by a colorimetric method. Cardiac hypertrophy was evaluated by measuring the heart weight:body weight and left ventricle + septum weight:body weight ratios. RESULTS: The SHRSP had markedly and significantly elevated G2 + M phase of the cell cycle. Treatment with perindopril resulted in a significant reduction in polyploidy in the SHRSP, whereas treatment with hydralazine and hydrochlorothiazide had no effect on the percentage of cells in the G2 + M phase of the cell cycle. The regression of polyploidy after treatment with perindopril was associated with a significant reduction in the concentration of Ang II and ACE activity, and with a significant regression of cardiac hypertrophy. Increased mitogenesis of cultured vascular smooth muscle cells from the SHRSP was not altered by treatment with perindopril. CONCLUSIONS: ACE inhibition reduces vascular smooth muscle polyploidy in large conduit arteries. This type of vascular protection is mediated by the reduced Ang II and possibly by increased kinins level, rather than by the hypotensive effect alone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Signal transduction mechanisms of the vasoconstriction in hypertension.

We tested the hypothesis that vascular smooth muscle in genetic hypertension is characterised by hypereactivity to vasoactive agonists, by abnormalities in Ca2+ handling and the phosphoinositide signalling system. Activation of these signal transduction mechanisms by noradrenaline and endothelin-1 was compared in isolated perfused tail arteries from adult hypertensive and normotensive Wistar Kyoto rats. Basal cytosolic Ca2+ was greater in arteries from hypertensive rats, but basal perfusion pressure and basal inositol phosphate accumulation were unchanged. Contractile responses and Ca2+ mobilisation after noradrenaline, but not endothelin-1, were enhanced in arteries from hypertensive rats. Total inositol phosphates accumulation was similar in hypertensive and normotensive rats after either noradrenaline or endothelin-1 stimulation. In both hypertensive and normotensive rats, for a given Ca2+ mobilisation, higher contractile responses and higher levels of inositol phosphates were observed after endothelin-1 than noradrenaline stimulation. In conclusion, changes in contractility associated with modifications in the Ca2+ handling between hypertensive and normotensive rats suggested that alterations in the signal-transduction system occur with hypertension. The different effects of endothelin-1 and noradrenaline could be related to interactions with other signalling pathways.

Animals↗