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Biomedical subjects

M C Sutter

Publications and source records attributed to M C Sutter.

At least 19 recordsLinked to original sources
PubMed1995

Lessons for atherosclerosis research from tuberculosis and peptic ulcer.

Knowledge of the causes of a disease is essential to the effective alteration of factors affecting the disease's incidence. The history of the medical understanding of tuberculosis and peptic ulcer shows that we may neglect to consider the contribution of microorganisms to long-term or recurring diseases. The author presents evidence that we may similarly be overlooking the role of microorganisms in atherosclerosis. A collaborative, comprehensive investigation of the role of microorganisms in atherosclerosis is needed to understand the cause of this disease.

Animals↗
PubMed1994

Effects of K+ channel openers on the vascular actions of human gamma globulin.

The aim of this study was to determine if the stimulatory action of human gamma globulin on the spontaneous activity of the rat mesenteric portal vein is due to decreased K+ conductance. Glibenclamide potentiated the action of human gamma-globulin on the portal vein by 45% and on its own had a concentration- and time-dependent biphasic (increase followed by a decrease) effect on the spontaneous activity of the portal vein. Diazoxide and pinacidil both inhibited the action of human gamma-globulin on the rat mesenteric portal vein. Levcromakalim (BRL 38227) potentiated the stimulatory action of human gamma-globulin on the integrated force of the spontaneous contractions of the rat mesenteric portal vein by 40% and 49% at concentrations of 0.5 and 5 microM, respectively. These studies suggest that human gamma-globulin can act by directly modulating a K+ channel.

Animals↗
PubMed1994

Wither, whether and whither pharmacology.

There has been considerable discussion over the last couple of years about the nature of pharmacology as a discipline and the training programmes for pharmacologists. Recently the British Pharmacological Society devoted a whole symposium to this important issue. In the UK in particular, pressure from government has nearly doubled the number of undergraduate students entering the university sector over the last five years, which has put considerable pressure on the teaching of essential practical courses for this experimental discipline. Similar pressures face the teaching of pharmacology in other countries and the situation, discussed here by Clive Page, Morley Sutter and Michael Walker, clearly has implications for academic pharmacology and the pharmaceutical industry. It is intended that the following article will stimulate both dialogue and positive action towards redressing this important problem.

Animals↗
PubMed1993

Stimulant effect of human gamma globulin on smooth muscle preparations.

The effects of human gamma globulin on the contractile activity of spontaneously active rat mesenteric portal vein and guinea-pig taenia caeci and quiescent rat aorta and guinea-pig trachea muscles were studied in vitro. Human gamma globulin significantly increased the contractile activity of the spontaneously active muscles with respect to both amplitude and frequency of contraction whereas it had no significant effect on the contractile activity of quiescent muscle preparations. These findings suggest that immunoglobulins directly modulate smooth muscle including vasculature by modifying the membrane electrical activity associated with the generation of spontaneous activity.

Animals↗
PubMed1993

Recent cardiovascular drugs from Chinese medicinal plants.

This paper describes the pharmacology of some recent cardiovascular drugs derived from plants used in Chinese traditional medicine. The groups of compounds discussed are benzylisoquinolines (several), tetrahydropyrazine (also called ligustrazine), rhynchophylline and hirsutine, ginkgolides and other PAF inhibitors, coumarins, and ginsenosides, plus a miscellaneous group; approximately 30 substances in all. The plant sources and the pharmacology are indicated for the drugs in each group. By far the most studied compounds are the benzylisoquinolines, especially tetrandrine. The types of pharmacological activity recently described for cardiovascular drugs from plants include calcium antagonism, adrenoceptor antagonism, antagonism of platelet activating factor (PAF), and the ability to act as antioxidants. Hundreds of chemicals have been isolated and identified as constituents of thousands of plants but the basic and clinical pharmacology is known for only a handful of these drugs. Much more research is needed, especially with regard to the pharmacology, both basic and clinical, of the pure chemicals derived from plants.

Cardiovascular Agents↗
PubMed1990

Effect of human plasma proteins on spontaneous contractile activity of rat mesenteric portal vein.

This study examines the effect of various plasma proteins from man on the spontaneous contractile activity of the rat portal vein. Albumin, gamma-globulin, alpha-globulin, beta-globulin (the major plasma proteins), and immunoglobulin IgG (the major immunoglobulin present in the gamma-globulin fraction) were obtained commercially. Mesenteric portal vein strips were prepared from rats and placed in a physiological salt solution in muscle baths for the measurement of longitudinal mechanical response. Portal veins exposed to albumin or gamma-globulin showed a dose-dependent increase in the spontaneous activity, whereas those exposed to alpha-globulin or alpha- and beta-globulin together showed a dose-dependent inhibition of spontaneous activity. Immunoglobulin IgG produced a dose-dependent increase in the spontaneous activity similar to that of gamma-globulin. The increased spontaneous activity produced by albumin was not prevented by ouabain but was inhibited by phentolamine. Spontaneous contractile activity was stimulated by albumin in the chemically (6-hydroxydopamine) denervated portal vein. These findings indicate that albumin acts in a manner similar to noradrenaline. The increased spontaneous activity caused by gamma-globulin (IgG) was inhibited by ouabain or verapamil. The effect of IgG was not dependent on alpha-adrenergic, cholinergic, histaminergic, serotoninergic, or renin angiotensin systems nor was it affected by removal of the endothelium. These observations may have implications in the pathophysiology of essential hypertension.

Alpha-Globulins↗
PubMed1989

Effect of plasma from hypertensive patients on contractile response of vascular smooth muscle from normotensive rat.

This study examines whether incubation with plasma from essential hypertensive patients increases the contractile activity of vascular smooth muscle from rats in response to noradrenaline (NA) and potassium (K+). Plasma samples were obtained from age- and sex-matched essential hypertensive patients and normotensive people. Vascular strips were prepared from aorta and portal veins of normotensive rats and placed in physiological solution in muscle baths for measurement of mechanical response. Aortic strips exposed to hypertensive plasma showed increased responsiveness to NA compared with normotensive plasma, but K+ caused an opposite effect. Portal vein exposed to normotensive or hypertensive plasma did not produce any response to NA, but the responsiveness produced in the presence of normotensive plasma to K+ was higher than that of hypertensive plasma. Portal vein exposed to normotensive plasma or hypertensive plasma showed a dose-dependent increase in the spontaneous activity up to 50% concentration of the plasma samples, but further increase in the concentration of plasma inhibited the spontaneous activity. Spontaneous activity at any given concentration of hypertensive plasma was significantly higher than that of normotensive plasma. The spontaneous activity in the presence of heated or unheated normotensive plasma or unheated normotensive serum was not significantly different from each other. These results indicate that the plasma factor from hypertensive patients, which alters the reactivity of vascular smooth muscle from normotensive rat, is present in the serum fraction and is not heat sensitive.

Animals↗
PubMed1988

Manganese can inhibit or potentiate contractile responses in mesenteric portal vein.

The effects of a number of agents believed to interfere with Ca were examined on contraction induced by noradrenaline (NA) or K in rat mesenteric portal veins. The organic calcium antagonists nifedipine, verapamil, methoxyverapamil, and felodipine slowly produced maximum inhibitory effects, nifedipine being fastest with a T1/2 of 20 min. In contrast, the inhibitory effects of Mn were immediate but disappeared on continued exposure of the tissue to Mn. After removal of Mn from the bath fluid, an above normal contraction was produced by K or NA. Measurement of Mn by atomic absorption spectrometry showed that the concentrations of EDTA-resistant Mn increased in parallel with the loss of inhibitory effects of Mn. This is consistent with an external inhibitory effect of Mn but a potentiating effect of Mn once it reaches an EDTA-inaccessible site. The potentiating effect of Mn was not seen with other ions such as Cd, Ni, Co, Mg, and La, which produced only inhibition of responses to NA or K. Contractile responses to Ba were examined in the absence of external Ca and it was found that the responses decreased with time. The presence of Mn not only prevented the loss of contractility but produced a marked increase in the response to Ba. Relaxation rates were also studied and it was found that Mn speeds the relaxation of contractures produced by NA or Ba as long as Mn is present in the bath fluid, but Mn slows relaxation when it is present (presumably) intracellularly. Mn does not alter relaxation rates of K contractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Ionic permeability and blood pressure.

The difficulty of establishing a causal relationship between any measured phenomenon and hypertension is emphasized. The literature concerning ion movements in tissues from hypertensive patients and animals is briefly reviewed. It is pointed out that the evidence (i) is conflicting concerning changes of permeability of red blood cells in patients with hypertension; (ii) is more consistent in leukocytes; and (iii) is virtually nonexistent regarding ionic permeability of blood vessels from man. A few studies suggest that permeability to calcium is altered in aortae from hypertensive animals and that concentrations of calcium in platelets are correlated with blood pressure in man. Some of our previously published work on red blood cells is then summarized which suggests that altered passive permeability to calcium exists in red blood cells from spontaneously hypertensive rats. Experiments are described using the calcium antagonists D-600 or felodipine to further study previously reported differences in calcium handling in blood vessels from spontaneously hypertensive rats. We could detect no difference in the effects of these calcium antagonists on blood vessels from hypertensive animals compared with controls. It is suggested that the finding of increased passive permeability to calcium in tissues from hypertensive animals is a lead worth pursuing.

Animals↗
PubMed1985

Chronic treatment of rats with D-600 causes a compensatory decrease in the calcium requirement for contractility of vascular smooth and cardiac muscles.

We studied the effects of chronic hypotensive treatment of normotensive Wistar rats (NWR) with methoxyverapamil (D-600) and hydralazine on in vitro contractile response of aortic strips, portal vein strips, and Langendorff-perfused hearts in normal (2.5 mM) and low (0.2 mM) calcium (Ca). Portal vein strips from rats treated with D-600, compared with the same strips from control and hydralazine-treated rats, developed greater spontaneous contractile activity in normal Ca and retained greater responses to norepinephrine (NE) and 80 mM K in low Ca. Aortic strips from all three groups of rats retained similar responses to NE and K in low Ca. Hearts from D-600-treated rats produced less intraventricular pressure (IVP) to isoproterenol (ISO) than hearts from control and hydralazine-treated rats in normal Ca but greater IVP to ISO than hearts from the other two groups of rats in low Ca. Thus, chronic treatment of NWR with D-600 but not with hydralazine resulted in the reduction of Ca requirement for contractile activities of the portal vein and the myocardium.

Animals↗
PubMed1983

Ethanol consumption and blood pressure.

Chronic ethanol consumption consistently resulted in mild hypertension in the male Wistar rats used in the present study. The ethanol-treated animals also have reduced 24-hour urinary output and significant sodium retention when compared to the controls. Total plasma volume was estimated using the technique of indicator dilution, and an increase of 20% was observed in the ethanol-treated animals. Vascular smooth muscle responsiveness to noradrenaline in vitro was not different between the two groups of animals. Therefore the blood pressure elevation in the ethanol-treated animals seems to be associated with sodium retention and plasma volume expansion, and probably is unrelated to altered vascular responsiveness.

Alcoholism↗
PubMed1983

Erythrocyte membrane properties of the chronic alcoholic rat.

There is growing evidence for essential or genetic hypertension to be associated with certain membrane abnormalities. We have published previous results on biochemical studies performed on erythrocyte membranes of the Okamoto-Aoki spontaneously hypertensive rat (SHR) and its normotensive control the WKY, reporting evidence of structural and functional alterations in the membranes. These changes could lead to increased calcium permeability and possibly compensatory increase in calcium pump activity that we observed concurrently. Chronic ethanol consumption resulted in mild hypertension in the rats used in the present study. The elevation in blood pressure is not associated with gross membrane changes in the erythrocyte. We noticed, however, that there is a slight elevation in the high affinity Ca2+/Mg2+-ATPase activities together with a trend towards higher osmotic fragility in the red cells of the ethanol-treated rats when compared with controls. These changes could be the result of concurrent reduction in plasma and membrane cholesterol contents also observed in the ethanol-treated animals.

Alcoholism↗
PubMed1983

Erythrocyte membrane abnormalities in hypertension: a comparison between two animal models.

Calcium-membrane interactions have been studied in two animal models of hypertension using the erythrocyte membrane as a model system. The Okamoto-Aoki strain of spontaneously hypertensive rats (SHR) was the first examined, and the activities of the Ca++/Mg++-ATPases in the membrane of SHR erythrocytes were found to be consistently higher than those of the normotensive controls (WKY), while other membrane enzymes such as Na+/K+-ATPase and acetylcholinesterase were not detectably altered. Erythrocyte membranes of the SHR also have a higher passive permeability to calcium as well as other functional and compositional differences when compared to those of the WKY. These findings suggest that the membrane alterations in the SHR may be related to an increased passive permeability to calcium, and a possibly compensatory increase in Ca++/Mg++-ATPase activity in these animals. The second animal model examined was the deoxycorticosterone/salt-induced hypertension (DOCA) in uninephrectomized rats. In DOCA rats with comparable degree of blood pressure elevation, none of the erythrocyte membrane abnormalities observed in the SHR were present, suggesting that the latter alterations are probably genetically determined and not a consequence of elevated arterial pressure.

Adenosine Triphosphatases↗
PubMed1982

The effects of chronic ethanol consumption on cardiac function in rats.

A pharmacological model of alcoholism in rats was developed by administering ethanol in their drinking water. This model has provided us with a convenient means to study the effects of chronic ethanol consumption on cardiac functional properties. Our "treated" animals consumed, on the average, an equivalent of 11.1 g/kg of absolute ethanol per day and had an average blood ethanol concentration of 26.9 mg/dL at the end of the 12-week treatment period. The Langendorff-perfused hearts from both treatment and control groups performed equally well mechanically when left to beat spontaneously, but under conditions of electrical pacing the contractile ability of hearts from the alcohol-treated animals deteriorated more rapidly. Dose-response relationships for isoproterenol (isopropylnoradrenaline, IPNA) showed that hearts from alcohol-treated animals did not respond as well as hearts from control animals at higher doses of IPNA. This trend was completely reversed in the presence of low external calcium where the hearts from alcohol-treated animals responded better at all IPNA concentrations. Our observations suggest that chronic alcohol consumption may give rise to alterations in calcium ion handling at the level of myocardial plasma membranes.

Alcoholism↗
PubMed1981

Differential effects of D 600 on contractile response of aorta and portal vein from spontaneously hypertensive rats.

To examine if Ca handling by vascular smooth muscles is altered in hypertension, the in vitro effect of D 600 was determined on noradrenaline-induced contractions of aortic and portal vein strips from spontaneously hypertensive rats (SHR) and Wistar Kyoto normotensive rats (WKY). In low (0.2 and 0.4 mM) Ca solutions, D 600 reduced the response to noradrenaline to a greater extent in aortic strips from SHR than in strips from WKY. In contrast, D 600 had less effect on the response to noradrenaline in portal vein strips from SHR than in strips from WKY in both normal and low Ca. Thus, portal veins from SHR are less dependent on external Ca compared to portal veins from WKY whereas aortae from SHR are more dependent on external Ca compared to aortae from WKY.

Animals↗