Morley C. Sutter

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.

Should we lower cholesterol as much as possible

Statins are portrayed as harmless drugs that almost everyone would benefit from, but little is known about the side effects at the high doses now being suggested

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.

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.

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.

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.

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.

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.