Renal functional, not morphological, abnormalities account for salt sensitivity in Dahl rats.

BACKGROUND: The kidney's role in the pathogenesis of salt-induced hypertension remains unclear. However, it has been suggested that inherited morphological renal abnormalities may cause hypertension. We hypothesized that functional, not morphological, derangements in Dahl salt-sensitive rats' kidneys cause NaCl retention that leads to hypertension accompanied by renal pathologic changes and proteinuria. METHOD: We studied hemodynamic, renal morphologic, and biochemical differences in Dahl salt-resistant and Dahl salt-sensitive rats fed low (0.05-0.23% NaCl) or elevated (1% NaCl) salt diets. RESULTS: We found similar hemodynamics, equal numbers of glomeruli, normal renal medullary interstitial cells and their osmiophilic granules, and cortical morphology in normotensive Dahl salt-resistant and Dahl salt-sensitive rats fed low dietary salt. Furthermore, aldosterone secretion, caused by angiotensin II infusion in normotensive rats fed 0.23% NaCl, was significantly less in Dahl salt-sensitive than Dahl salt-resistant rats. Increasing NaCl to 1% caused renal vasoconstriction without changing cyclic GMP excretion in Dahl salt-sensitive rats; in Dahl salt-resistant rats, cyclic GMP increased markedly and renal vascular resistance remained unchanged. On 1% NaCl for 9 months, Dahl salt-sensitive rats developed marked hypertension, severe renal vasoconstriction, glomerulosclerosis, tubulointerstitial abnormalities, and marked proteinuria; hypertension resulted from increased total peripheral resistance, as occurs in essential hypertensive humans. No hemodynamic or renal pathologic changes occurred in Dahl salt-resistant rats, and proteinuria was minimal. CONCLUSION: We conclude that renal functional, not morphological, abnormalities cause salt sensitivity in Dahl rats.

NASA--has its biological groundwork for a trip to Mars improved?

In a 1991 editorial in The FASEB Journal, Robert W. Krauss commented on a recent report of the Presidential Advisory Committee on the Future of the U.S. Space Program (Augustine report). He concluded that, although a manned mission to Mars with life sciences as the priority was endorsed by the Committee, it failed to deal realistically with one huge gap; biological sciences have never been given high priority. According to Krauss, this left a void that will cripple, perhaps fatally, any early effort to ensure long-term survival on any mission of extended duration. The gap included insufficient flight time for fundamental biological space research and insufficient funds. Krauss expressed his opinions 15 years ago. Have we better knowledge of space biology now? This question becomes more acute now that President George W. Bush recently proposed a manned return to the moon by 2015 or 2020, with the moon to become our staging post for manned missions to Mars. Will we be ready so soon? A review of the progress in the last 15 years suggests that we will not. Because of the Columbia disaster, flight opportunities for biological sciences in shuttle spacelabs and in Space Station laboratories compete with time for engineering problems and construction. Thus, research on gravity, radiation, and isolation loses out to problems deemed to be of higher priority. Radiation in deep space and graded gravity in space with on board centrifuges are areas that must be studied before we undertake prolonged space voyages. Very recent budgetary changes within National Aeronautics and Space Administration threaten to greatly reduce the fundamental space biology funds. Are we ready for a trip to Mars? Like Krauss 15 years ago, I think not for some time.

Role of dietary salt in hypertension.

Certain things have not changed since my colleague and I last reviewed the role of dietary salt in hypertension [Haddy, F.J., Pamnani, M.B., 1995. Role of dietary salt in hypertension. Journal of the American College of Nutrition 14, 428-438]. Over half of hypertensives are still salt sensitive, i.e., they respond to a high NaCl intake with a rise in blood pressure. This can be ameliorated by restricting NaCl intake, supplementing potassium intake, and consuming diuretics. Some things have changed. We now have more insight into mechanism; we suspected that volume expansion and endogenous Na(+),K(+)-ATPase inhibitors were the connection between excessive salt intake and the hypertension, but we were not certain as to the nature of the inhibitors. Now it appears that the inhibitors are steroids released from the adrenal gland and are members of the cardenolide family, e.g., ouabain, and the bufadienolide family, e.g., marinobufagenin. This presents new possibilities in therapy, including antibodies to these agents and competitive inhibitors to their binding to Na(+),K(+)-ATPase.

Role of potassium in regulating blood flow and blood pressure.

Unlike sodium, potassium is vasoactive; for example, when infused into the arterial supply of a vascular bed, blood flow increases. The vasodilation results from hyperpolarization of the vascular smooth muscle cell subsequent to potassium stimulation by the ion of the electrogenic Na+-K+ pump and/or activating the inwardly rectifying Kir channels. In the case of skeletal muscle and brain, the increased flow sustains the augmented metabolic needs of the tissues. Potassium ions are also released by the endothelial cells in response to neurohumoral mediators and physical forces (such as shear stress) and contribute to the endothelium-dependent relaxations, being a component of endothelium-derived hyperpolarization factor-mediated responses. Dietary supplementation of potassium can lower blood pressure in normal and some hypertensive patients. Again, in contrast to NaCl restriction, the response to potassium supplementation is slow to appear, taking approximately 4 wk. Such supplementation reduces the need for antihypertensive medication. "Salt-sensitive" hypertension responds particularly well, perhaps, in part, because supplementation with potassium increases the urinary excretion of sodium chloride. Potassium supplementation may even reduce organ system complications (e.g., stroke).

Protective effects of dietary potassium chloride on hemodynamics of Dahl salt-sensitive rats in response to chronic administration of sodium chloride.

BACKGROUND: Dietary potassium supplementation decreases blood pressure and prevents strokes in humans, and prevents strokes and renal damage in Dahl salt-sensitive (DSS) rats. OBJECTIVE: To study the effects of various concentrations of dietary potassium chloride (KCl) on the hemodynamics of Dahl salt-resistant (DSR) and DSS rats receiving a 1% sodium chloride (NaCl) diet for 8 months, to determine whether there is an optimal dietary concentration of KCl that minimizes increases in blood pressure and causes least impairment of blood flow in the brain and kidneys. METHODS AND RESULTS: We found a biphasic effect on hemodynamic parameters as a function of dietary KCl in DSS rats of the Rapp strain fed 1% NaCl with increasing dietary KCl (0.7, 2.6, 4 and 8%). After 8 months receiving a diet containing 1% NaCl and 0.7% KCl, DSS rats had mean arterial pressures (MAP), plasma volumes, cardiac outputs and renal and cerebral vascular resistances that were significantly increased compared with those of DSR rats receiving the same diet. With a 2.6% KCl diet, all these parameters were significantly reduced compared with those in DSS rats fed the 0.7% KCl diet and were similar to those in DSR rats fed 2.6% KCl. Total peripheral resistance in DSR and DSS rats was similar on all diets. When KCl was increased to 4 and 8%, MAP, plasma volume, cardiac output and renal vascular resistance progressively increased in DSR and DSS rats, without changing total peripheral resistance. These changes paralleled increases in plasma aldosterone, which resulted from adrenocortical stimulation by the increasing dietary KCl; however, cerebral vascular resistance of DSR and DSS rats decreased significantly with a 4% KCl diet, despite increased aldosterone and sodium retention. Only DSS rats fed a 2.6% KCl diet had hemodynamics similar to those of DSR control rats fed the same diet, and hyperaldosteronism, sodium retention and increased plasma volume did not occur. CONCLUSION: 'Optimal' dietary KCl (2.6%) prevents hypertension and preserves cerebral and renal hemodynamics in DSS rats fed a diet containing 1% NaCl for 8 months, which causes hypertension when dietary KCl is limited or excessive.