Biomedical subjects
E E Muirhead
Publications and source records attributed to E E Muirhead.
Multiple access diffusion chamber and the cultivation of liver cells.
Explore the source record for details and available documents.
Electrophoretic precipitin test on cellulose acetate.
Explore the source record for details and available documents.
Renomedullary antihypertensive principle in renal hypertension.
Explore the source record for details and available documents.
The in vitro culture of embryonic chicken heart cells.
Explore the source record for details and available documents.
Elevation of peripheral vascular resistance in renoprival hypertension.
Explore the source record for details and available documents.
An inexpensive, multipurpose immunoelectrophoretic chamber.
Explore the source record for details and available documents.
Streptomycin-specific antibody coincident with a developing warm autoantibody.
The presence of an antibody with specificity against streptomycin-sensitized red blood cells in the serum of a patient with tuberculous pericarditis is reported. Hemolysis and significant anemia were absent. The antibody appeared to develop together with an evolving warm autoantibody, but was clearly separable from the latter. The streptomycin-specific antibody was "penicillin-like" by being totally neutralized in the presence of streptomycin. Red blood cells had to be separately sensitized with streptomycin prior to incubation with the antibody. The antibody cross-reacted with neomycin-sensitized cells and was also neutralized by the presence of neomycin. In addition, a possible cross-reactivity of the streptomycin-specific antibody and the warm autoantibody is suggested. The association of a drug-induced antibody and autoimmune antibody of IgG type is most unusual. In our experience, we have encountered only one similar example.
Antihypertensive polar renomedullary lipid, a semisynthetic vasodilator.
Explore the source record for details and available documents.
Hemodynamic and antihypertensive effects of captopril, an orally active angiotensin converting enzyme inhibitor.
Captopril inhibits angiotensin II formation and bradykinin degradation in vivo. Eleven patients with essential hypertension (EH) and four patients with renovascular hypertension (RVH) were treated with captopril for periods ranging from 3 days to 12 months. All patients had a diastolic blood pressure (DBP) over 95 mm Hg after receiving a placebo for 3 days. Captopril given in ascending doses (10-1000 mg/day) caused normalization of blood pressure in all but three patients, one with severe RVH whose pressure fell 11%, one patient with severe EH, whose pressure fell 27%, and one with EH whose blood pressure fell 8.5%. The average control DBP in patients with EH was 113.7 +/- 5.5 (SE) mm Hg and fell to 89.9 +/- 3.6 mm Hg (p less than 0.001), while DBP in patients with RVH fell from 110.7 +/- 7.6 mm Hg to 94.5 +/- 8.2 (p less than 0.005). All patients were studied in balance on a 100 mEq sodium (Na) diet. Plasma renin activity (PRA) versus 24-hour urinary Na excretion increased sevenfold during therapy while converting enzyme activity fell by about one half. The magnitude of the blood pressure response was not related to control PRA. Cardiac output was estimated by echocardiography during placebo administration and during maintenance therapy with captopril. A significant change was not observed. Total peripheral resistance fell an average of 18.9% (p less than 0.05) in 11 of the 13 patients in whom the measurement could be made. It is concluded that captopril effectively lowers blood pressure in patients with EH or RHV by reducing total peripheral resistance.
Renomedullary deficiency in partial nephrectomy-salt hypertension.
Partial nephrectomy-salt hypertension (PN-SH) of the rat is associated with Na volume loading. As the hypertensive state evolves, the renomedullary interstitial cells (RIC) of the renal nubbin undergo major changes, decreasing significantly in number while the remaining ones exhibit degenerative changes. The antihypertensive action of the RIC in the renal nubbin, as measured by transplants of fragmented papillae into hypertensive recipients, virtually disappears as the hypertension develops. The changes in the RIC occur whether vascular disease of the kidney is or is not overtly present. It is suggested that deficiency of the antihypertensive action of the RIC allows the prohypertensive effects of Na volume loading to operate without proper control. Thus, the sustained hypertensive state of this model does not appear to be due solely to volume expansion. Rather, it appears due to a combination of the effects of Na and volume and a renomedullary deficiency of hormonal type. The specific cause(s) of the changes in the RIC was not determined. It seems evident that it is related to the high salt intake since the partial nephrectomy procedure without the added salt load did not alter the appearance of the RIC.
Antihypertensive functions of the kidney: Arthur C. Corcoran memorial lecture.
Explore the source record for details and available documents.
Alkyl ether analogs of phosphatidylcholine are orally active in hypertensive rabbits.
1-0-alkyl ethers of phosphatidylcholine having an acetoyl in the second position were derived from fresh renal tissue. The main ether so derived had a 16:0 chain. The C16:0 alkyl ether was synthesized de novo. The renally derived and the synthetic ether exerted a similar and powerful antihypertensive action in hypertensive rabbits when given orally in divided doses. This action was prolonged, requiring more than 60 hours after the last input of the compound for recovery of the arterial pressure. As these ethers exerted their antihypertensive action, there was no evidence of adverse effects. Noteworthy was the failure of these depressor compounds to cause renin release. Diuresis-kaliuresis did not occur. A suggestion of sodium retention was noted.
Analogs of phosphatidylcholine: alpha-adrenergic antagonists from the renal medulla.
Antihypertensive polar renomedullary lipid (APRL), a conglomerate of 1-0-alkyl-2-acetoyl-glycero-3-phosphocholine analogs, ws tested in 4- to 6-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats using microcirculatory techniques. APRL (0.5 ug/ml), when added to the solution bathing the cremaster muscle, caused significant changes in the diameter, red blood cell velocity, and blood flow in both groups of rats, for arterioles and venules. Arteriolar changes in diameter were significantly greater (p less than 0.05) in SHR than in WKY. Micropipette application of APRL indicated a dose-dependent response for arterioles and venules in both groups. Moreover, the potent nature of this compound was demonstrated. Relative potency of APRL given intravenously was tested in 10- to 12-week-old SHR and WKY. The response curve was shifted significantly to the left for SHR (p less than 0.01). APRL interaction with known controllers of blood flow was tested in SHR. Blockade of cholinergic, beta-adrenergic, or histaminergic receptors did not inhibit APRL action. blockade of prostaglandin or bradykinin synthesis did not prevent depression of blood pressure by APRL. APRL (40 ug/kg) inhibited (p less than 0.001) the pressor response to norepinephrine (1-10 ug/kg) but not to angiotensin II (4 ug/kg). The present study provides direct evidence that APRL is a vasodilator with increased potency in SHR hypertension. The acute vascular response may be mediated by alpha-adrenergic antagonism.
Degranulation of renomedullary interstitial cells during reversal of hypertension.
It was demonstrated earlier that the renal venous effluent of one-kidney, one clip hypertensive rats contained a vasodepressor lipid resembling the antihypertensive neutral renomedullary lipid (ANRL), following unclipping and as the arterial pressure (MAP) was lowered. Consequently, the sham-unclipped (clip-intact) and the unclipped kidney (CK and UCK) were studied by electronmicroscopy and morphometrically (Weibel's techniques). Renomedullary interstitial cells (RIC) of the CK had abundant granules. The collecting duct (CD) had tall lining cells containing pale granules and displayed intercellular channels. Following unclipping, the RIC degranulated and the CD cells became flattened, lost their pale granules, and the intercellular channels disappeared as the MAP decreased. These changes were evident by EM appearance and volume density measurements. The renopapillary changes occurred as the kidney secreted the ANRL-like substance into the blood.
Cardiovascular effects of antihypertensive polar and neutral renomedullary lipids.
Two antihypertensive lipids can be extracted from fresh renal medulla. One is polar (the antihypertensive polar renomedullary lipid, or APRL) and the other is nonpolar (the antihypertensive neutral renomedullary lipid, or ANRL). APRL and ANRL differ in their biologic activities: APRL in bolus intravenous injections causes a very rapid decline in the arterial pressure (AP) while ANRL, after a lag of 2 minutes, causes a slower decline in AP. APRL increases heart rate and sympathetic activity. ANRL decreases heart rate and sympathetic activity. ANRL appears to convert to APRL, under certain in vitro circumstances, suggesting that the structure of the two molecules is related. ANRL and APRL appear in the renal venous effluent after unclipping; biologically, ANRL seems dominant. The renal venous effluent of the unclipped isolated kidney lowers the HR and sympathetic activity of the normal rat. Unclipping degranulates the renomedullary interstitial cells (RIC). The antihypertensive effect of unclipping appears due to the secretion of ANRL and APRL by the kidney. It is concluded that ANRL seems to be the antihypertensive hormone of the RIC.
Antihypertensive polar and neutral renopapillary lipids. Which is a hormone?
Two antihypertensive lipids can be derived from the renal papilla, the antihypertensive polar (APRL) and the antihypertensive neutral (ANRL) renomedullary lipid. The renal venous effluent of the unclipped kidney contains both ANRL and APRL. This effluent lowers the arterial pressure (AP) of the normal rat when infused i.v. As it lowers the AP the heart rate (HR) and sympathetic nerve activity (SNA) are depressed. ANRL infused i.v. also lowers HR and SNA as it depresses the AP. Conversely, APRL elevates HR and SNA as it lowers the AP. Thus, of the two lipids in the renal venous effluent after unclipping, ANRL appears to be dominant. APRL, however, in the renal venous effluent could potentiate the action of ANRL. The net effect of these observations is to support the view that ANRL is an antihypertensive hormone liberated by the kidney after unclipping. The renomedullary interstitial cells (RIC) degranulate after unclipping. ANRL can be derived from these cells. Thus, the RIC, cells known to exert an endocrine-type antihypertensive function, may well be the source of ANRL in the renal venous effluent after unclipping. The hormonal action of ANRL appears as a major cause of the lowering of the AP after unclipping. It is not known what factors modulate the RIC endocrine system. There is a suggestion that angiotensin may be one of these factors based on the ineffectiveness of these cells toward retarding hypertension when the circulating plasma angiotensin level is high, and their effectiveness when the circulating plasma angiotensin level is low.
Regional hemodynamic effects of antihypertensive renomedullary lipids in conscious rats.
Renomedullary tissue has been proposed to exert an antihypertensive endocrine-like action. The antihypertensive polar renomedullary lipids (APRL) and neutral renomedullary lipids (ANRL) are potential mediators of this action. We evaluated the blood pressure and regional hemodynamic responses to APRL administered peripherally (i.v.) and to the central nervous system (CNS) in normal rats and rats with sinoaortic deafferentation (SAD) to remove baroreflex buffering. Rats were chronically instrumented with Doppler flow probes for measurement of mesenteric, renal, and hind-quarter vascular resistance, with arterial pressure and intravenous catheters, and with lateral cerebroventricular cannuli for intracerebroventricular (i.c.v.) administration. Intravenous APRL (0.01 to 1.0 micrograms) produced a dose-dependent decrease in blood pressure, tachycardia, and dilation of all vascular beds studied. The dose-response relationships were shifted to the left in SAD animals. APRL administered i.c.v. had no effect on intact or SAD rats. Pressor and regional vasoconstrictor responses to norepinephrine, angiotensin, and vasopressin were markedly reduced in SAD animals during constant infusion of APRL. In a second group of conscious SAD animals instrumented for blood pressure and heart rate measurements, intravenous ANRL (500 micrograms) decreased both arterial pressure (-45 +/- 16 mm Hg) and heart rate (-50 +/- 16 bpm). When given i.c.v., however, ANRL (10-100 micrograms) had no significant effect on resting blood pressure or heart rate. These studies suggest that APRL and ANRL produce no significant cardiovascular effects that are mediated through the CNS. However, both lipids are potent depressor agents, and APRL exhibits a strong peripheral vasodilator action and nonspecifically reduces reactivity to vasoconstrictor agents.