Local effects of hypokalemia on coronary resistance and myocardial contractile force

Brace, R. A.; Anderson, DK; Wt, Chen; Scott, J.A.; Fj, Haddy

doi:10.1152/ajplegacy.1974.227.3.590

Cited by 54 publications

(17 citation statements)

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“…Both theoretical 8 and experimental 8 " 10 evidence supports the concept that inhibition of (Na + + K + ) ATPase can increase the contractile force of vascular smooth muscle. The mechanism of action could involve the compensatory inhibition or reversal of a sodium-calcium exchange pump due to increased levels of intracellular sodium.…”

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confidence: 69%

“…The mechanism of action could involve the compensatory inhibition or reversal of a sodium-calcium exchange pump due to increased levels of intracellular sodium. 8 This would result in elevated intracellular calcium (Ca), potentiating contraction. The term "digitalis-like factor" has been used to describe this proposed substance since its physiological action, inhibition of (Na + + K + ) ATPase and potentiation of vascular smooth muscle contraction, would be similar to that of the cardiac glycoside class of drugs.…”

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confidence: 99%

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Increased circulating levels of an endogenous digoxin-like factor in hypertensive monkeys.

Gruber¹,

Rudel²,

Bullock³

1982

Hypertension

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SUMMARY An endogenous, immunoreactive digoxin-like factor (endoxin) was measured in the plasma of nonhuman primates with hypertension. Both normotensive and hypertensive rhesus monkeys had levels of endoxin that significantly correlated with their systolic or diastolic blood pressure. Vervet monkeys with experimentally produced chronic Goldblatt hypertension had significantly elevated endoxin, but not plasma renin. These data suggest that increased plasma endoxin may be a contributing factor in the development of hypertension. (Hypertension 4: 348-354, 1982) KEY WORDS • digitalis-like factor natriuretic hormone sodium-potassium ATPase inhibition S EVERAL investigators have proposed that a circulating inhibitor of cardiovascular sodium-potassium adenosine triphosphatase ([Na + + K + ] ATPase) may be a causative factor in some forms of hypertension.1 " 4 The initial evidence for a (Na + + K + ) ATPase defect came from data indicating a blunted vasodilatory effect of potassium infusions in both experimental 516 and clinical essential hypertension. 7 This was followed by direct measurement of the cardiovascular enzyme in models of renovascular hypertension. 1These experiments revealed an inhibition of cardiovascular (Na + + K + ) ATPase, an effect that could be duplicated in vitro by application of cardiac glycosides. These data suggested the presence of a circulating inhibitor of the enzyme.

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confidence: 69%

mentioning

confidence: 99%

Increased circulating levels of an endogenous digoxin-like factor in hypertensive monkeys.

Gruber¹,

Rudel²,

Bullock³

1982

Hypertension

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“…The direct effects of elevated potassium concentration on vascular smooth muscle appear to result from two separate actions of this ion: the well-known depolarizing effect and a second, hyperpolarizing effect resulting from stimulation of an electrogenic pump. The net effect of potassium on the smooth muscle cell has, in fact, been interpreted quantitatively as the sum of opposing actions of the ion (27,30,39). In support of this concept is the fact that the vascular smooth muscle relaxation induced by potassium can be eliminated or converted to a constriction by the administration of ouabain (10,12,25).…”

Section: Dulingmentioning

confidence: 99%

Effects of potassium ion on the microcirculation of the hamster.

Duling¹

1975

Circulation Research

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The vasoactive properties of potassium were assessed in the microcirculation of the hamster cremaster muscle and the muscular and epithelial portions of the hamster cheek pouch. Tissues were transilluminated and suffused with a physiological salt solution whose potassium concentration varied from 0 to 20 mM. Vessel diameters were measured and normalized as a percent of the control diameter (± SE) observed during exposure to 4.7 mM K + . Altering the potassium concentration in the suffusion solution caused a transient vascular response. The peak changes in the vascular diameter of the arterioles supplying striated muscle varied directly with the suffusion solution potassium concentration from a minimum of 78 ± 3% in 0 mM K + to 155 ± 15% in 15 mM K". Vascular diameter increases were sustained for the full 5-minute test period only in 15 mM K+. In the epithelial portions of the cheek pouch, only the constrictor component of the potassium response was observed. The data indicate that potassium is sufficiently potent to participate in initiating functional hyperemia in striated muscle and might cause as much as a 6.3-fold increase in flow. Functional hyperemias exceeding approximately 3 minutes cannot be due to potassium ion, since the dilation induced by this agent is transient.• Cells contain a large store of labile potassium that can be released by various stimuli such as muscle contraction and hypoxia (1-9). Many investigators have shown that potassium at the increased concentrations observed in venous blood during exercise and hypoxia can relax smooth muscle both in vivo (5)(6)(7)(8)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and in vitro (21-31). Therefore, this ion. may be important in the local control of blood flow. However, further quantification of the reactivity of resistance vessels to the ion must be carried out before accurate estimates of the importance of potassium in blood flow regulation can be made. These data can be obtained by studying microvessel responses to alterations in suffusion solution potassium concentrations, but such experiments have only been performed on pial vessels (11,16,17). Furthermore, no data are currently available showing the temporal response pattern of microvessels during variations in potassium concentration. These data are of particular interest in view of the transient potassium ion release during functional hyperemia in striated muscle (7,8) and the transient vascular smooth muscle response to potassium both in vitro (26-32) and in vivo (10). A preliminary report of this work was presented at the Fall Meeting of the American Physiological Society, August, 1974. This work was done during Dr. Duling's tenure as an Established Investigator of the American Heart Association.Received September 20, 1974. Accepted for publication June 4, 1975. I have therefore studied the responses of the arterioles of the hamster cremaster muscle and cheek pouch to changes in the potassium concentration of a superfusion solution. The aims of the experiment were to: (1) estab...

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“…3 and in low-renin experimental 4 - 6 and human essential 79 hypertension. It has been hypothesized that this factor, through inhibition of NKA as with the cardiac glycosides or with decreased [K + ], constricts blood vessels, 10 enhances vasoconstrictor responses to agonists, 11 increases cardiac contractility (dP/dt), 12 and raises blood pressure (BP). 13 Numerous investigators have attempted to isolate this endogenous NKA inhibitor.…”

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confidence: 99%

Chronic blood pressure effects of bufalin, a sodium-potassium ATPase inhibitor, in rats.

Pamnani

Chen²,

Yuan³

et al. 1994

Hypertension

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Endogenous Na + ,K + -ATPase inhibitors may have a role in the mechanism of low-renin hypertension. Two such compounds have been characterized: ouabain from human plasma and resibufogenin from toad plasma. Previously, we examined the acute effects of ouabain and bufalin (which has the same structure as resibufogenin except for one H + ) in normal rats. Bufalin raised blood pressure, but ouabain had little effect. In contrast, given chronically, ouabain substantially increased blood pressure in normal rats and 70% reduced renal mass rats on a salt-free diet. We have now examined the chronic effects of bufalin in rats. Normal rats received 14.8 ng/kg per day bufalin or an equimolar dose of ouabain intraperitoneally for 6 weeks; 70% reduced renal mass rats also received 14.8 fig/kg per day bufalin. Another group of normal rats received 29.6 jig/kg per day bufalin intraperitoneally for 6 weeks. Respective control animals received vehicle.In contrast to ouabain, blood pressure did not increase in normal rats receiving the 14.8 ^tg dose of bufalin. However, normal rats receiving 29.6 /ig bufalin and 70% reduced renal mass rats receiving 14.8 fig bufalin developed significant increases in blood pressure. Increases in blood pressure were associated with decreases in myocardial Na + ,K + -ATPase activity and correlated with increased plasma Na + ,K + -ATPase inhibitory activity. Thus, although bufalin is a more potent pressor agent than ouabain when both agents are given acutely, ouabain is at least as potent a vasopressor agent as bufalin when given chronically. Thus, both are pressor agents, more so in the presence of reduced renal mass, when given chronically in the rat. 13 Numerous investigators have attempted to isolate this endogenous NKA inhibitor. However, only two steroid NKA inhibitors have been purified and chemically characterized -resibufogenin, a bufodienolide derivative in toad skin and plasma, 14 and a substance with the same basic structure as ouabain from human plasma. 15 In an earlier study 16 designed to determine whether such endogenous inhibitors in fact produce the above cardiovascular changes, we compared the acute effects of equimolar doses of commercially available bufalin (aglycone, identical to resibufogenin except for one H + ) and ouabain (Fig 1) in normal rats. Bufalin infused intravenously into anesthetized rats increased BP, dP/dt, heart rate, urine volume, and urinary sodium excretion. When applied to tail arteries from normal rats in vitro, bufalin depolarized vascular smooth muscle cell membrane potentials. Although equimolar doses of ouabain caused the same directional changes in all parameters except heart rate and membrane potentials, the magnitudes of these changes were always less than those produced by bufalin (ouabain had no effect on heart rate or vascular smooth muscle cell membrane potentials). In fact, ouabain actually decreased BP at higher doses. In contrast, in a subsequent study 17 we found that ouabain given chronically raised BP in both normal and 70% reduced ...

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Local effects of hypokalemia on coronary resistance and myocardial contractile force

Cited by 54 publications

References 0 publications

Increased circulating levels of an endogenous digoxin-like factor in hypertensive monkeys.

Increased circulating levels of an endogenous digoxin-like factor in hypertensive monkeys.

Effects of potassium ion on the microcirculation of the hamster.

Chronic blood pressure effects of bufalin, a sodium-potassium ATPase inhibitor, in rats.

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