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F Haddy

Publications and source records attributed to F Haddy.

8 recordsLinked to original sources
PubMed1991

Cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating/Na-K-ATPase-inhibiting activity of plasma and hypothalamus in reduced renal mass hypertension.

Plasma from normal humans and rats on a high sodium intake, and from patients and rats suffering from hereditary hypertension has an increased cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating/Na-K-ATPase inhibiting activity. The hypothalamic content of this activity is also increased by a high sodium intake and in the spontaneously hypertensive rat (SHR). Using cytochemical techniques, the ability of plasma and the hypothalamus of reduced renal mass hypertensive rats to stimulate G6PD activity and to inhibit Na-K-ATPase was measured. The mean G6PD-stimulating capacity of the plasma from the hypertensive and normotensive groups of rats was 351 +/- 67 and 11.42 +/- 1.98 G6PD-stimulating units/mL respectively (P less than .001). The time courses of the ability of plasma from a hypertensive and a normotensive rat to inhibit fresh tissue Na-K-ATPase after 2, 4, 6, and 8 min of exposure demonstrated that the hypertensive rat plasma had a greater capacity to inhibit Na-K-ATPase. The mean G6PD-stimulating capacity of the hypothalamus from the hypertensive and normotensive groups of rats was 252,263 +/- 147,958 X 10(3) and 6.38 +/- 2.35 X 10(3) G6PD-stimulating units per hypothalamus, respectively (P less than .01). It is proposed that the raised concentration of cytochemically detectable G6PD-stimulating/Na-K-ATPase-inhibiting substance in both genetic and nongenetic forms of hypertension may be a manifestation of a communal hypertensinogenic mechanism. Thus, the raised plasma concentration would have a direct peripheral vascular constricting effect and the high hypothalamic concentration would be responsible for a central nervous hypertensinogenic effect.

Animals↗
PubMed1991

Effects of bufalin on norepinephrine turnover in canine saphenous vein.

Abundant experimental data suggest that an endogenous digitalislike factor is responsible for some essential hypertension. Some forms of hypertension have also been associated with increased levels of catecholamines. We therefore designed experiments to investigate the role of digitalislike factors in the regulation of norepinephrine turnover in the neurovascular junction. We chose bufalin, an amphibian-derived compound that shares many of the physiological properties postulated as characteristic of digitalislike compounds, as a model of the mammalian compound. In vitro experiments in canine saphenous veins showed that, in addition to inhibiting norepinephrine uptake, bufalin increased norepinephrine overflow by an amount larger than could be explained solely by uptake inhibition. The effect of bufalin on norepinephrine overflow is inhibited by tetrodotoxin, which suggests a dependence of this response on Na+ influx through the neuronal membranes. We propose that Na+,K(+)-ATPase inhibition resulting in neuronal depolarization is responsible for the augmented norepinephrine turnover caused by bufalin and that these indirect effects of norepinephrine on the cardiovascular system may play a role in the etiology of hypertension.

Animals↗
PubMed1989

Hemodynamic effects of bufalin in the anesthetized dog.

Studies in Lichstein's laboratory suggest that the endogenous digitalislike substance implicated in low renin hypertension might be a steroidal dienolide derivative. If this is true, the bufadienolides should block potassium vasodilation and enhance norepinephrine vasoconstriction, constrict blood vessels, raise blood pressure, and produce natriuresis and diuresis. We have therefore examined these parameters while infusing bufalin (aglycone), a bufadienolide, intrabrachially and intravenously in the anesthetized dog. Intrabrachial infusion of 5-25 micrograms/min with brachial arterial blood flow held constant at 100 ml/min produced a dose-dependent increase in perfusion pressure with rapid onset and offset, a progressive decrease in the vasodilator response to intrabrachial injection of 1 ml iso-osmotic potassium chloride solution (but not to acetylcholine), and an increase in the vasoconstrictor response to intrabrachial injection of 0.1 microgram norepinephrine. Intravenous infusion at 5-50 micrograms/min produced a dose-dependent increase in systemic arterial blood pressure, rate of change of ventricular pressure (dP/dt), and after the highest dose, cardiac irregularities. Natriuresis and diuresis were not observed. Thus, bufalin does in fact have some of the physiological properties required to be considered a candidate for the digitalislike substance found in low renin hypertension.

Anesthesia↗
PubMed1984

Periventricular forebrain mechanisms for blood pressure regulation.

Periventricular forebrain regions participate in body fluid and cardiovascular regulatory mechanisms that are intimately related to neural participation in experimental hypertension. Ablation of preoptic-hypothalamic periventricular tissue surrounding the anteroventral third ventricle (AV3V) disrupts both angiotensin (AngII) and sodium regulatory mechanisms and prevents experimental hypertension in either renin-dependent or -independent models. When AV3V is spared, and central AngII pressor mechanisms are interrupted by subfornical organ ablation or anterior hypothalamic knife cuts, renin-dependent but not renin-independent models of hypertension are prevented. Volume-expanded models of hypertension may be mediated by a natriuretic hormone that also inhibits the sodium-potassium pump in vascular smooth muscle, resulting in increased vasoconstriction. Volume expansion-induced release of this humoral ATPase inhibitor is attenuated in rats with AV3V lesions. In the renin-independent, reduced renal mass model, development of hypertension is correlated with increased plasma levels of sodium-potassium pump inhibitor. AV3V ablation blocks both the hypertension and the increase in humoral ATPase inhibitor. Thus, Thus, central angiotensin pressor and natriuretic mechanisms overlap in AV3V, and prevention of renin-dependent and volume-dependent models of experimental hypertension by AV3V ablation appears linked to disruption of these functionally separable systems.

Angiotensins↗
PubMedDate not supplied

The sodium-potassium pump in volume expanded hypertension.

Decreased arterial Na+-K+ pump and cardiac Na+, K-+ATPase activities have now been demonstrated in several types of experimental volume expanded hypertension. The changes are not secondary to elevated pressure since they also occur in veins and right ventricle where the pressure is not elevated. Decreased arterial Na+-K+ pump activity can be reproduced by acute volume expansion of the normal rat and plasma extracts from this rat suppress pump activity when applied to arteries from another rat. Suppression of Na+-K+ pump activity in arteries, veins and heart, with ouabain for example, leads to increased contractile activity. Thus the volume expansion, reduced pump activity, and hypertension appear to be causally related through an ouabain-like humoral agent. Certain other evidence suggests that the pump defect extends to the sympathetic nerve endings, thereby reducing the efficiency of neural compensatory mechanisms.

Animals↗