Renin-angiotensin system prostaglandins

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

Dzau VJ, Packer M, Lilly LS, Swartz SL, Hollenberg NK, Williams GH. Prostaglandins in severe congestive heart failure. Relation to activation of the renin-angiotensin system and hyponatremia. N Engl J Med 1984 310(6) 347-52. 

McGiff, J.C. (1980). Interactions of prostaglandins with the kallikrein-kinin and renin-angiotensin systems. Clin. Sci, 59, 105s-116s... 

Speckart, P., Zia, P., Zipser, R. and Horton, R. (1977). The effect of sodium restriction and prostaglandin inhibition on the renin-angiotensin system in man. Clin. Endocrinol Metab., 44, S32-S37... 

Although the regulation of the secretion of vasopressin appeared simple a few decades ago and seemed to involve only the activation of the osmoreceptor, it is now clear that a number of factors not related to osmolarity also regulate vasopressin secretion. They include blood volume receptors, systemic barorecep-tors and hormones such as catecholamine, prostaglandins, adrenocortical hormones, thyroid hormones, and the renin-angiotensin system. 

Nephrotoxins that cause tubular necrosis may indirectly induce vasoconstriction and reduce renal blood flow. These changes may occur because alteted delivery of solutes to the distal nephron affects the action of prostaglandins and the renin-angiotensin system. 

Prednisolone can cause an abrupt rise in proteinuria in patients with nephrotic syndrome. A placebo-controlled study in 26 patients aged 18-68 years with nephrotic syndrome has clarified the mechanisms responsible for this (163). Systemic and renal hemodynamics and urinary protein excretion were measured after prednisolone (125 mg or 150 mg when body weight exceeded 75 kg) and after placebo. Prednisolone increased proteinuria by changing the size-selective barrier of the glomerular capillaries. Neither the renin-angiotensin axis nor prostaglandins were involved in these effects of prednisolone on proteinuria. 

Abbreviations NSAID = nonsteroidal anti-inflammatory drugs, PG = prostaglandin, RBF = renal blood flow, GFR = glomerular filtration rate,HTN = hypertension, DM = diabetes mellitus, = potassium, RAA = renin-angiotensin- aldosterone, CHF = congestive heart failure, AGE = angiotensin-converting enzyme, SLF = systemic lupus erythematosis. 

Other unusual conditions that suggest aldosterone excess or deficiency but are not connected to the renin-angiotensin-aldosterone system include Liddle s syndrome (pseudo hyper aldosteronism),which resembles primary aldosteronism clinically, but aldosterone production is low and hypertension is absent and Barttefs syndrome,which involves a prostaglandin-mediated renal potassium wasting and renal chloride handling defect, in which both aldosterone concentrations and renin activities are elevated. In renal tubular acidosis and pseudohypoaldosteronism, the clinical picture of hypoaldosteronism is seen concurrent with greater-than-normal concentrations of aldosterone. 

The relationship of the renin-angiotensin-aldosterone system to bradykinin and prostaglandin production is shown in Figure 30. 

In addition, the kidneys have direct endocrine functions. Because they are a major site of synthesis of several hormones, including erythropoietin and 1,25-dihydroxy-cholecalciferol, the kidneys indirectly influence the regulation of blood pressure and vasopressor activity via the renin-angiotensin, prostaglandins, and kallekrein-kinin systems, which exert a regulatory effect on water and electrolyte homeostasis (Harris 1992 Parekh et al. 1993 Gonzalez et al. 1998 Campean et al. 2003 see also Chapters 6 and 10). 

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