Richard L. Tannen

Indomethacin potentiates the vasoconstrictor actions of angiotensin II in normal man.

The blood pressure response to graded infusions of angiotensin II was assessed under control conditions and following short term (16 hour) indomethacin treatment utilizing normal men equilibrated on a constant diet of normal sodium and potassium content. Although basal mean blood pressure was unchanged, the increase in blood pressure with all rates of angiotensin II infusion ranging from 200 to 1000 ng/min was significantly greater with indomethacin treatment. Pre-infusion body weight and plasma renin activity were similar under the two conditions. These results suggest that prostaglandins modulate the systemic vasoconstrictor effects of angiotensin II.

Effects of Potassium on Blood Pressure Control

Potassium depletion causes hypotension in normotensive animals and can lower the blood pressure in hypertensive animals and humans. Potential mechanisms for this hypotensive effect include a decrease in aldosterone levels, a decrease in vasopressin, and decreased responsiveness to the pressor effects of angiotensin II. The decreased response to angiotensin II could result from increased prostaglandin production, receptor occupancy, or a decrease in angiotensin II receptor affinity. A high potassium intake has no effect on blood pressure in normotensive animals and humans, but lowers blood pressure in those with hypertension. Mechanisms for this antihypertensive effect include natriuresis with sodium depletion, a decrease in plasma renin activity, an alteration in the neurogenic components of blood pressure regulation, and effects on resistance vessels related either to a high potassium concentration or to a decrease in the number of angiotensin II receptors.

Vasopressin-Resistant Hyposthenuria in Advanced Chronic Renal Disease

Abstract Eleven of 13 patients with far advanced chronic renal disease of diverse etiologies were found to have urine that remained hypotonic to plasma in spite of the administration of a supramaxi...

Nephropathy Associated with Heat Stress and Exercise

Excerpt Heat stress and exercise may result in severe medical consequences in both military and civilian populations. In World War I, Willcox (1) reported 462 heatstroke deaths in 1 month among Bri...

Chronic hypoxia induces proliferation of cultured mesangial cells: role of calcium and protein kinase C

The effect of hypoxia on the proliferation of cultured rat mesangial cells was examined. To evaluate the underlying signaling mechanisms, the roles of intracellular calcium ([Ca2+]i) and protein kinase C (PKC) were determined. Quiescent cultures were exposed to hypoxia (3% O2) or normoxia (18% O2), and [3H]thymidine incorporation, cell number, [Ca2+]i, and PKC were assessed. Mesangial cells exposed to 28 h of hypoxia exhibited a significant increase in [3H]thymidine incorporation followed by a significant increase in cell number at 72 h in comparison with respective normoxic controls. Hypoxia induced a biphasic activation of PKC, reflected by translocation of the enzyme activity from cytosol to membrane at 1 h, a return to baseline at 4 and 8 h, with subsequent reactivation from 16 to 48 h. In addition, hypoxia-induced proliferation was prevented by a PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Cells exposed to hypoxia produced progressive increases in resting [Ca2+]i from 15 to 60 min which remain sustained up to 24 h of examination. Verapamil significantly prevented the hypoxia-induced proliferation, and both verapamil treatment and incubations in a calcium-free medium for 1 h blocked the hypoxia-induced stimulation of [Ca2+]i as well as PKC. These results provide the first in vitro evidence that chronic hypoxia induces proliferation of cultured glomerular mesangial cells, which is mediated by the stimulation of [Ca2+]i and the subsequent activation of PKC.The effect of hypoxia on the proliferation of cultured rat mesangial cells was examined. To evaluate the underlying signaling mechanisms, the roles of intracellular calcium ([Ca2+]i) and protein kinase C (PKC) were determined. Quiescent cultures were exposed to hypoxia (3% O2) or normoxia (18% O2), and [3H]thymidine incorporation, cell number, [Ca2+]i, and PKC were assessed. Mesangial cells exposed to 28 h of hypoxia exhibited a significant increase in [3H]thymidine incorporation followed by a significant increase in cell number at 72 h in comparison with respective normoxic controls. Hypoxia induced a biphasic activation of PKC, reflected by translocation of the enzyme activity from cytosol to membrane at 1 h, a return to baseline at 4 and 8 h, with subsequent reactivation from 16 to 48 h. In addition, hypoxia-induced proliferation was prevented by a PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Cells exposed to hypoxia produced progressive increases in resting [Ca2+]ifrom 15 to 60 min which remain sustained up to 24 h of examination. Verapamil significantly prevented the hypoxia-induced proliferation, and both verapamil treatment and incubations in a calcium-free medium for 1 h blocked the hypoxia-induced stimulation of [Ca2+]ias well as PKC. These results provide the first in vitro evidence that chronic hypoxia induces proliferation of cultured glomerular mesangial cells, which is mediated by the stimulation of [Ca2+]iand the subsequent activation of PKC.

Comparison of countershock with direct and alternating current in external cardiac defibrillation. Report of a case.

THE combined use of external cardiac massage and external electric defibrillation, as developed by Kouwenhoven et al.1 and Zoll and his associates,2 has added new dimensions to the resuscitation of...