Summary
Renomedullary antihypertensive function was studied in rats in which the renal medulla was chemically damaged either by chronic ingestion of high doses of aspirin (the rats were treated for 6 months before the experiment with aspirin at 300 mg/kg/day) or by a single injection of bromethylamine hydrobromide (BEA) (50 mg/rat, i.v., two months before the experiment). The results were compared to those from control, nontreated rats. When placed on a high salt intake (1% NaCl solution was offered instead of drinking water), the rats with aspirin-induced renomedullary damage and the controls did not develop hypertension during the 12-week period of salt loading, while the animals treated with BEA developed high blood pressure (systolic pressure over 20 kPa) by the sixth week. In the second experiment, renal medullae taken from control, aspirin-treated, and BEA-treated rats were transplanted to rats with chronic one-kidney one-clip hypertension, and the potency of medulla taken from the three different groups in lowering blood pressure in the hypertensive recipients was compared. A significant decrease in blood pressure of about 4–5 kPa was observed in the hypertensive rats which received transplants of medullae taken from control and aspirin-treated rats; whereas no significant change in blood pressure was observed in the hypertensive rats which received transplants of medullae taken from BEA-treated rats, or which were sham-transplanted. The results indicate that the deficiency of renomedullary antihypertensive function is an event conducive to the development of salt hypertension in rats, i.e., an increase in blood pressure in response to salt loading was observed only in animals in which the antihypertensive function of the medulla was decreased, as determined by the inability of renomedullary transplants to lower blood pressure in hypertensive recipients. Furthermore, the present data indicate that aspirin-induced renomedullary damage does not abolish renomedullary antihypertensive function; and thus the notion that hypertension associated with aspirin abuse nephropathy results from aspirin-induced renomedullary deficiency appears to be unlikely.
Zusammenfassung
Durch chronische Ernährung mit großen Dosen Aspirin (300 mg/kg/Tag) im Laufe von 6 Monaten vor den Versuchen oder durch einzelne Injektion von Bromethylaminhydrobromid (BEA-50 mg/kg, i.v., zwei Monate vor den Experimenten) waren Ratten chemisch geschädigt. Die antihypertonische Wirkung des Nierenmarkes wurde an solchen Ratten untersucht. Die Ratten unter Aspirin, wenn zugleich mit Salz überlastet (statt Trinkwasser war ihnen 1%ige NaCl-Lösung gegeben worden), zeigten Nierenmarkschädigungen; aber der Blutdruck dieser sowie der Kontrollgruppe nach 12 Wochen Salzüberlastung war noch immer normal. Der Blutdruck der Tiere, die BEA-Injektionen bekommen haben, war schon nach sechs Wochen Salzüberlastung erhöht. In zweiter Versuchsreihe wurde das Nierenmark der Ratten aus Kontroll-, Aspirin- und BEA-Gruppe den Ratten mit Goldblatt-Hypertonie transplantiert und die Kraft der Hochblutdruckerniedrigung in verschiedenen Gruppen hypertonischer Empfänger verglichen. Die hypertonischen Ratten, die das Nierenmarktransplantat aus Kontroll- und Aspirin-Gruppe erhalten haben, zeigten einen Blutdruckfall von 4–5 kPa. Der Blutdruck des Nierenmarktransplantates aus BEA-Ratten blieb unverändert. Das Resultat zeigt, daß die Insuffizienz des Nierenmarkes, eine antihypertonische Wirkung auszulösen, ein wichtiger Faktor für die Entwicklung der Hypertonie der Ratten ist, d. h., eine Blutdruckerhöhung als Antwort zur Salzüberlastung nur an Tieren, die eine erniedrigte antihypertonische Nierenmarkfunktion zeigten, bemerkt wurde, wie die Unfähigkeit des Nierenmarktransplantates, den Blutdruck in hypertonischen Empfängern zu erniedrigen. Außerdem zeigen die Angaben dieser Versuche, daß durch Aspirin hervorgerufene Nierenmarkschädigungen antihypertonische Nierenmarkfunktion nicht auslöschen. Das alles spricht gegen die Idee, daß die Hypertonie, welche die Aspirin-Nephropathie begleitet, die Folge der durch Aspirin hervorgerufenen Nierenmarkinsuffizienz ist.
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References
Bohman, S. O.: The ultrastructure of the renal medulla and the interstitial cells. In: The renal papilla and hypertension. A. K. Mandal and S. O. Bohman (Eds.). pp. 7–33. Plenum Press (New York 1980).
Heptinstall, R. H., D. C. Salyer, W. R. Salyer: The effect of chemical ablation of the renal papilla on the blood pressure of rats with and without silver-clip hypertension. Amer. J. Pathol.78, 297–308 (1975).
Hultengren, N.: Renal papillary necrosis. A clinical study of 103 cases. Acta Chir. Scand.277 (suppl.), 1–26 (1961).
Kincaid-Smith, P.: Parenchymatous disease of the kidney and hypertension. In: Hypertension. J. Genest, E. Koiw and O. Kuchel (Eds.), pp. 794–814, McGraw Hill (New York 1977).
Lee, J. B.: The inter-relationship between renal prostaglandins and blood pressure regulation. Amer. J. Med. Sci.263, 334–346 (1970).
Leonards, J. R., C. R. Heisler: Maintenance of life in bilaterally nephrectomized dogs and its relation to malignant hypertension. Amer. J. Physiol.167, 553–562 (1951).
Manthorpe, T.: The effect on renal hypertension of subcutaneous isotransplantation of renal medulla from normal and hypertensive rats. Acta Path. Microbiol. Scand. Sect. A.81, 725–733 (1973).
Molland, E. A.: Experimental renal papillary necrosis. Kidney Int.13, 5–14 (1978).
Muirhead, E. E., J. A. Stirman, F. Jones: Renal autoexplantation and protection against renoprival hypertensive cardiovascular disease and hemolysis. J. Clin. Invest.39, 266–272 (1960).
Muirhead, E. E., G. B. Brown, G. S. Germain, B. E. Leach: The renal medulla as an antihypertensive organ. J. Lab. Clin. Med.76, 641–651 (1970).
Muirhead, E. E., B. E. Leach, L. W. Byers, B. Brooks, E. G. Daniels, J. W. Hinman. Antihypertensive neutral renomedullary lipids (ANRL). In: Kidney Hormones. J. W. Fisher (Ed.). pp. 485–506. Academic Press (New York 1971).
Muirhead, E. E., B. Brooks, W. L. Brosius. Renomedullary deficiency. A permissive factor in renoprival hypertension. Arch. Pathol.95, 77–80 (1973).
Muirhead, E. E., J. A. Pitcock: Evidence for an involvement of the renal papilla in hypertension. In: The renal papilla and hypertension. A. K. Mandal and S. O. Bohman (Eds.). pp. 35–61. Plenum Press (New York 1980).
Murray, G., R. G. Wyllie, G. S. Hill, P. W. Ramsden, R. H. Heptinstall: Experimental papillary necrosis of the kidney. I. Morphologic and functional data. Amer. J. Pathol.67, 285–302 (1972).
Prewitt, R. L., B. E. Leach, L. W. Byers, B. Brooks, W. E. M. Lands, E. E. Muirhead: Antihypertensive polar renomedullary lipid, a semisynthetic vasodilator. Hypertension1, 299–306 (1979).
Solez, K., R. J. D'Agostini, R. A. Buono, N. Vernon, A. L. Wang, P. M. Finer, R. H. Heptinstall: The renal medulla and mechanisms of hypertension in the spontaneously hypertensive rat. Amer. J. Pathol.85, 555–568 (1976).
Sušić, D., J. C. Sparks, D. Kentera: The renin-angiotensin system in rats with hereditary hydronephrosis. Pflügers Arch.358, 265–274 (1975).
Sušić, D., J. C. Sparks, E. A. Machado: Salt-induced hypertension in rats with hereditary hydronephrosis: the effect of renomedullary transplantation. J. Lab. Clin. Med.87, 232–239 (1976a).
Sušić, D., J. C. Sparks, E. A. Machado: Renomedullary deficiency. A contributory factor in the pathogenesis of experimental renal hypertension. Experientia.32, 354–355 (1976b).
Sušić, D., J. C. Sparks, E. A. Machado, D. Kentera: The mechanism of renomedullary antihypertensive action: haemodynamic studies in hydronephrotic rats with one-kidney renal clip hypertension. Clin. Sci. Mol. Med.54, 361–367 (1978).
Sušić, D., D. Kentera: Role of the renal medulla in the resistance of rats to salt hypertension. Pflügers Arch.384, 283–285.
Sušić, D.: Studies on the mechanism of the renomedullary antihypertensive action. In: The renal papilla and hypertension. A. K. Mandal and S. O. Bohman (Ed.). pp. 63–76. Plenum Press, (New York 1980).
Tobian, L., S. Azar: Antihypertensive and other functions of the renal medulla. Trans. Assoc. Am. Physicians.84, 281–290 (1971).
Wallenstein, S., C. L. Zucker, J. L. Fleiss: Some statistical methods useful in circulation research. Circulat. Res.47, 1–9 (1980).
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Sušic, D., Mujović, S. & Kentera, D. The effect of chemical damage to the renal medulla on its antihypertensive function. Basic Res Cardiol 78, 8–18 (1983). https://doi.org/10.1007/BF01923189
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DOI: https://doi.org/10.1007/BF01923189