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Biomedical subjects

E E Muirhead

Publications and source records attributed to E E Muirhead.

At least 37 records · Page 2Linked to original sources
PubMed1989

The renal antihypertensive endocrine function: its relation to cytochrome P-450.

Unclipping the Goldblatt hypertensive rat lowers the blood pressure by cells in the renal papilla, the renomedullary interstitial cells (RIC), secreting a hormone that is part of a vasodilator system. A vasodilator, termed medullipin I, can be extracted from the renal papilla. Medullipin I and the renal venous effluent following unclipping have identical biologic properties. Medullipin I appears to be the agent secreted by the kidney following unclipping. Both medullipin I and the renal venous effluent must traverse the liver to be active. Medullipin I is converted in the liver to its active form, medullipin II. The blood pressure-lowering effect of both medullipin I and the renal venous effluent after unclipping are blocked by SKF 525A, the inhibitor of cytochrome P-450. The relation of the kidney to the liver was tested using the rate of decline of the blood pressure after unclipping as an index of the endocrine antihypertensive function of the kidney--acceleration of the decline being considered as increased function, decrease of the decline as decreased function. Five compounds: BW755C, phenobarbital, ketoconazole, eicosatetraynoic acid (ETYA) and butylated hydroxytoluene (BHT), and two manipulations: uretero-caval anastomosis (UCA) and removal of the liver from the circulation were used followed by unclipping. BW755C, inhibitor of both cyclo-oxygenase and lipoxygenase, potentiated the antihypertensive function to a maximum. It is reasoned that inhibition of the first two pathways of arachidonic acid metabolism potentiates the third pathway, the cytochrome P-450 pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Renal and circulatory effects of medullipin I, as studied in the in-vivo cross-circulated isolated kidney and intact Wistar-Kyoto (WKY) rat.

The renal medulla harbours powerful humoral antihypertensive mechanisms, as earlier explored in unclipping experiments on renal hypertensive rats or in normotensive isolated kidneys cross-circulated at increased perfusion pressures from 'donor rats', in which renal function also seemed to be affected. Injection of the renomedullary factor medullipin I (Med I; formerly ANRL) mimics these haemodynamic responses, and Med I seems to be one of the most important mediators of the depressor effects. The present study was performed to analyse further the haemodynamic and, particularly, the renal effects of Med I, using anaesthetized intact WKY rats and constant-pressure perfused (90 mmHg) isolated WKY kidneys, cross-circulated by these intact 'donor' rats. Mean arterial pressure (MAP), heart rate (HR) and renal function were followed for one 30-min period before and two 30-min periods after injection of 1 mg Med I (M; n = 7) or an equal volume of saline as control (C; n = 13). In the intact 'donor' WKY, MAP and HR remained largely constant in C during the three periods, being 126 +/- 5, 125 +/- 5, and 120 +/- 5 mmHg, while MAP fell in the M group after Med I, from 121 +/- 5 to 107 +/- 7 and 107 +/- 5 mmHg (P less than 0.05), and also HR tended to decrease in M. Renal resistance (RR) fell while renal plasma flow (RPF) and glomerular filtration rate (GFR) increased significantly (P less than 0.05) after Med I in the M donor rats despite their MAP reduction. However, in the constant-pressure perfused, cross-circulated kidneys the RR, RPF and GFR changes were clearly more pronounced (P less than 0.01) and also diuresis, natriuresis, osmolar excretion and osmolar clearance increased significantly after Med I (P less than 0.01). In conclusion, the present results support the view that Med I not only has important and long-lasting depressor effects but also affects renal function in important ways, inducing vasodilatation and increasing GFR, RPF, diuresis and sodium-osmolar excretion.

Animals↗
PubMed1988

Glycosaminoglycans of the rat renomedullary interstitium: ultrastructural and biochemical observations.

The rat renal papillary interstitum which contains abundant proteoglycans is a unique area important in renal function. These proteoglycans were studied ultrastructurally by ruthenium red fixation and staining and phosphate-buffered fixation before and after enzyme digestion. A tissue culture of rat renomedullary interstitial cells, the predominant cell of the renal papillary interstitum, was studied for its ability to synthesize proteoglycans and the proteoglycans were then analyzed. Tissue slices of whole rat renal inner medulla were also evaluated for their synthetic ability. In combination, these studies indicate that the dominant glycosaminoglycan is hyaluronic acid. The tissue culture of rat renal medullary interstitial cells synthesized glycosaminoglycans and on analysis, hyaluronic acid was found to be the chief glycosaminoglycan secreted by the renomedullary interstitial cells. Combined with the removal of the proteoglycans from tissue by leech hyaluronidase and testicular hyaluronidase, this suggests that the dominant glycosaminoglycan is hyaluronic acid. Hyaluronic acid is also synthesized by the intact papilla confirming the findings with the tissue culture. However, in addition, sulfated glycosaminoglycans were also synthesized by the intact papilla, presumably the product of the noninterstitial components of the papilla.

Animals↗
PubMed1987

The reno-hepatic axis of blood pressure control: further studies.

A reno-hepatic axis of blood pressure (BP) control has been proposed primarily by two developments: the lag period between the injection of the antihypertensive neutral renomedullary lipid (ANRL) into the vena cava and the beginning of the drop of the BP is significantly reduced by injection of this lipid into the portal vein; and a reno-portal shunt (RPS) accelerates markedly the drop of the BP following unclipping the Goldblatt hypertensive rat. In the present studies, three maneuvers were performed: perfusion of the isolated, blood-drained rat liver with plasma containing ANRL and delivery of the plasma into the jugular vein of a hypertensive rat; injection of captopril, establishment of a RPS of a hypertensive rat (one-kidney, one-clip) followed by unclipping; and establishment of a RPS in a normal rat. The blood-drained liver was capable of decreasing significantly the lag period of ANRL. Captopril did not potentiate the antihypertensive action of the kidney when RPS was coupled with unclipping. Following the RPS, the BP of the normal rat dropped modestly over a 3-hour period. These results further support the concept of reno-hepatic axis of BP control.

Animals↗
PubMed1987

Selachyl alcohol as an oral antihypertensive agent: a preliminary note.

Selachyl alcohol (SA) is a mono-oleyl glyceryl ether. It has certain biologic activities similar to those of the antihypertensive neutral renomedullary lipid (ANRL) derived from the renal papilla and its renomedullary interstitial cells (RIC). These include a vaso-depressor effect following bolus injection and a requirement for hepatic activation for the development of biological activity. In view of this similarity to ANRL, it appeared worthwhile to test the antihypertensive action of SA when given via the GI tract. Accordingly, pure SA was given either by gavage or by tube into the stomach or duodenum of one-kidney, one-clip hypertensive rats (5-10 mg per dose). The role of hepatic activation was demonstrated by comparing the BP response to bolus injection of SA and ANRL with and without the presence of an intact circulation to the liver. Administration of SA via the GI tract resulted in a significant decline in BP without tachycardia or weight loss. In the absence of a circulation to the liver, neither SA nor ANRL was active. SA appears to be an effective antihypertensive agent when given via the GI tract.

Animals↗
PubMed1986

The liver converts the antihypertensive hormone of the kidney. The renohepatic axis.

The antihypertensive neutral renomedullary lipid, derived from the renal papilla, causes a vasodepressor effect when injected into a peripheral vein, such as the inferior vena cava, after a lag period of 1 to 2 minutes. The blood pressure tracing is skewed (cuplike effect). The lag period is significantly reduced after injection of the antihypertensive lipid into the portal vein. The vasodepressor configuration (cuplike) is the same whether the lipid is injected into the vena cava or portal vein. Removal of the liver from the circulation prevents the depressor effect. Thus, passage through the liver is essential for antihypertensive lipid activity. Renoportal shunting of blood potentiates the antihypertensive function of the kidney after unclipping in the one-kidney, one clip hypertensive rat. Lack of a hepatic circulation prevents the antihypertensive function of the kidney after unclipping. Antihypertensive neutral renomedullary lipid and the renal venous effluent after unclipping have the same biological behavior. We conclude that antihypertensive neutral renomedullary lipid is a promolecule, the putative prohormone of the renal papilla and its renomedullary interstitial cells. The liver converts the antihypertensive prohormone of the kidney to an active antihypertensive substance. A renohepatic axis of blood pressure control appears to exist.

Animals↗
PubMed1986

Renal medullary system of blood pressure control.

The renal medulla contains cells in its papillary portion, the renomedullary interstitial cells (RIC), that secrete a blood pressure-controlling hormone. This hormone system has been identified by classic types of experiments as developed by Bayliss and Starling, Goldblatt, Byrom and Dodson and Berthold. The antihypertensive neutral renomedullary lipid is the putative hormone. This hormonal system is antagonized by angiotensin II. It antagonizes the blood pressure (BP) elevating effects of salt.

Angiotensin II↗
PubMed1985

B2 bradykinin receptor-like binding in rat renomedullary interstitial cells.

A particulate fraction from cultured rat renomedullary interstitial cells (RRIC) was prepared for bradykinin (BK) binding studies. Incubation of three radiolabeled BK analogs, [125I-Tyr1]kallidin, [125I-Tyr5]-BK, and [125I-Tyr8]-BK, with the particulate fraction resulted in degradation of these peptides. Assay conditions which prevented hydrolysis of these radiolabeled kinins were determined. Under these conditions, direct binding studies were performed with [125I-Tyr1]kallidin (TlK) as the radioligand. BK binding affinity, apparent Kassoc. = 1.3 X 10(9) M-1, and specificity, determined with 51 BK analogs, were consistent with those expected of a B2 BK receptor.

Animals↗
PubMed1985

The morphology and antihypertensive effect of renomedullary interstitial cells derived from Dahl sensitive and resistant rats.

The renomedullary interstitial cell (RIC) has been implicated in the antihypertensive action of the kidney. This cell has been isolated in tissue culture and shown to have an antihypertensive action in several models of experimental hypertension. Morphometric studies of RIC in vivo from Dahl rats sensitive and resistant to the hypertensive effects of high-salt diets indicate major differences between the RICs. These cells were therefore isolated from salt-sensitive and salt-resistant strains of rat, grown, and maintained in tissue culture. Major morphologic differences between the two cell lines were noted and persisted for multiple tissue culture passages. The cells from resistant animals were larger and had more lipid granules. These differences were similar to those seen in vivo. In short-term experiments these cells were compared for their antihypertensive effect. The two cell lines were injected subcutaneously into two groups of hypertensive recipient rats, one group of Dahl salt-sensitive rats on a high-salt diet and one group of Wistar rats subjected to the one-kidney, one-clip Goldblatt procedure. In both cases differences were noted between the cell lines. These data support the concept that differences between the Dahl salt-sensitive and salt-resistant rats may be related to variations in their RIC.

Animals↗
PubMed1984

Morphometric studies on the rat renal papilla of resistant and sensitive strains in partial nephrectomy salt hypertension.

The renomedullary interstitial cell (RIC) was studied morphometrically in the partial nephrectomy-salt (Chanutin-Ferris) model of hypertension. The RIC were compared in four strains of rat, two of them being resistant to the induction of this form of hypertension and two of them being sensitive. The Dahl salt-resistant (R/JR) rat was compared to a commercial Sprague-Dawley (SD) strain, and a Wistar derived strain discovered in Belgrade by Susic and Kentera (WB) was compared to a commercial Wistar strain (W). In both studies, resistance and sensitivity correlated well with the state of the RIC before the experimental procedure, the resistant strain having more numerous and better granulated RIC than the sensitive strain. It may therefore be possible to predict salt-resistance or sensitivity in rats by morphological examination of the RIC.

Animals↗
PubMed1982

Blockade of alpha-adrenergic receptors by analogues of phosphatidylcholine.

The experimental evidence reviewed in this article suggests that the kidneys may have an additional function in regulating blood pressure besides their role in controlling both blood volume by urine formation and the relative state of vasoconstriction by the renin-angiotensin system. That is, the kidneys may have an additional influence upon the vasculature of a hormonal vasodilating system. The interstitial cells of the renal medulla appear to be mediating this activity and lipid compounds have been extracted from the renal medulla which display depressor activity. One such compound, the antihypertensive polar renomedullary lipid (APRL), has been demonstrated to consist of specific alkyl ether analogues of phosphatidylcholine. The vascular responses to these compounds include vasodilation of both arterioles and venules, rapid lowering of arterial blood pressure with little or no tachycardia, increased depressor activity in hypertensive animals, and blockade of vascular smooth muscle alpha 1-adrenergic receptors. Most recently, APRL and a synthetic analogue, 1-0-octadecyl-2-acetyl-sn-glycero-3-phosphorylcholine, have been used to demonstrate alpha-adrenergic receptor blockade on a smooth muscle cell line (DDT1) by radioligand assays. This action may be due to the insertion of these compounds into cell membranes causing subsequent steric interactions and blockade of the alpha-adrenergic receptor.

Acetylation↗