E. Eric Muirhead

Antihypertensive activity of an alkyl ether analog of phosphatidylcholine.

Summary An alkyl ether analog of phosphatidylcholine was prepared from choline plasmalogen of fresh beef heart by reducing the alk-1-enyl moiety to an alkyl group and by hydrolyzing the sn -2 acyl moiety and replacing it with an acetoyl group. The basis for preparing and testing this compound resulted from experience with antihypertensive lipids derived from the renal medulla and from experience with ether lipid biochemistry. The alkyl lipid analog was found to possess powerful antihypertensive properties in the one-kidney, one-clip hypertensive rats when given either intravenously or orally. This activity induced acute and prolonged depressor effects. These actions were similar to those of a glycerophosphate obtained from fresh renal medulla and designated as APRL (antihypertensive polar renomedullary lipid).

Malignant hypertension in blacks: Malignant intrarenal arterial disease as observed by light and electron microscopy

Volhard and Fahr recognized that hypertensive intrarenal vascular disease could be divided into two groups corresponding to the clinical states of benign and malignant hypertension. Since that time, numerous papers on malignant hypertension, primarily dealing with European derived populations, have emphasized fibrinoid necrosis of small arteries and arterioles as the lesion of malignant hypertension, although some have also recognized a myxoid intimal lesion as characteristic. Today in the United States, however, a significant proportion of malignant hypertension occurs in blacks. In the present study, patients have lacked fibrinoid necrosis of arterioles and only rarely have had some atypical necrosis of small arteries. The prominent, but not pathognomonic, lesion in this series is a myxoid intimal thickening of small arteries consisting of smooth muscle cells, acid mucopolysaccharides, basement membrane-like materal, collagen, and other amorphous and unidentified material, probably plasma derived.

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.

Long‐Term Captopril Therapy: Evolving Hemodynamic Effects

Abstract: Nine patients with resistant hypertension received captopril for 12 months. Five received captopril alone, four required additional therapy. In the former, mean blood pressure fell from 109 ± 4.2 mm Hg to 84 ± 7.5 mm Hg (P < 0.025) after seven days. A rise to 101 ± 19 mm Hg was noted at six and 12 months. Total peripheral resistance fell at seven days but returned to levels above control at six and 12 months. Cardiac index was 3.21 ± 0.55 liters/min/m2 before treatment, 3.27 ± 0.56 liters/min/m2 at seven days, and 2.17 ± 4.0 liters/min/m2 (P < 0.025) at 12 months. However, forearm blood flow rose from subnormal levels during the 12 months of observation, suggesting a persistent effect on the arterioles of the extremities. Plasma converting enzyme activity was significantly reduced at seven days but was above control levels at six and 12 months. However, plasma renin activity remained elevated, and plasma aldosterone concentration was significantly reduced. The fall in mean blood pressure was not related to the change in plasma converting enzyme activity in patients receiving captopril alone (five patients) or with diuretic (two patients). In the presence of beta‐adrenergic blockade and volume depletion (two patients), changes in mean blood pressure appeared to be related to changes in converting enzyme activity. The data suggest that patients with essential hypertension whose blood pressure was not adequately controlled by previous medications may initially respond to captopril with a fall in blood pressure and total peripheral resistance. However, in certain individuals, these effects diminish with time despite addition of diuretics and beta‐adrenergic receptor blocking agents.

The Relationship of the Renal Medulla to the Hypertensive State

The kidney appears to relate to the hypertensive state via two opposing actions, what Braun-Menendez termed the prohypertensive and antihypertensive renal actions.1 According to current views, the prohypertensive renal action results primarily from (1) activation of the renal pressor system(s) (mainly the renin-angiotensin system), and (2) failure of the kidney to prevent Na-volume loads (because of disease or absence or the excessive action of mineralocorticoids, primarily aldosterone). It is our view that the antihypertensive renal action also results from a dual renal effect, namely (1) the relief of Na-volume loads by the excretory process and (2) activation of a renal antipressor system existing primarily in the renal medulla. Moreover, it is proposed that this antipressor system resides, to a great extent, in the renomedullary interstitial cells (RIC).