Renal and endocrine response to saline infusion in essential hypertension.

Abstract

SUMMARY To assess the contribution of the renln-angiotensin-aldosterone system and renal hemodynamics to acute renal sodium handling in essential hypertension we studied 21 subjects who had essential hypertension (16 with normal renin, 5 with low renin) and 9 normal subjects. All were in balance on a 10 mEq sodium intake before receiving a small sodium load, 60 mEq intravenously over 1 hour. Hypertensive subjects with low renin showed the anticipated exaggerated natriuresis, which was transient and occurred without a rise in blood pressure. Natriuresis in hypertensive subjects with normal renin was either normal or blunted; delayed sodium excretion occurred in a subset, along with delayed suppression of the renin-angiotensin-aldosterone system by the saline load. Neither renal plasma flow nor glomerular filtration rate changed during the saline load. After 72 hours of converting enzyme inhibition with enalapril, renal plasma flow increased substantially more in the subjects with a blunted renin response and their natriuretic response to the sodium load returned to normal. These results indicate that when prior sodium intake is controlled, large sodium loads are avoided, and low renin hypertension is removed as a confounding variable, blunted rather than exaggerated natriuresis is the common feature of essential hypertension. Equally well documented has been the sensitivity of hypertension to sodium intake. 43 It has been difficult to reconcile the two phenomena -accelerated sodium excretion and sensitivity of the hypertension to sodium intake -in a single pathogenetic sequence, in which sodium is responsible for the hypertension. Without exception, however, the acute sodium load employed in earlier studies has been very large, and with few exceptions, the state of sodium balance before administration of the sodium load was uncontrolled. One goal of this study was to assess the rate of sodium Received April 4, 1985; accepted August 27, 1985. excretion after a much more physiological sodium load, 60 mEq, or about the quantity of sodium in a typical meal, in subjects whose sodium balance was controlled before administration of the sodium load. In response to a large sodium load, suppression of the renin-angiotensin-aldosterone system is delayed in some subjects with normal renin and essential hypertension.6 These subjects also have disordered angiotensin-mediated control of renal perfusion and aldosterone release with shifts in sodium balance.7 A second goal of this study was to examine the response of the renin system to a much smaller sodium load and to relate the magnitude of renin suppression to the rate of sodium excretion following the sodium load. Our working premise was that sodium excretion must reflect, at least in part, the state and responsiveness of the renin-angiotensin-aldosterone system and the renal blood supply.Because earlier studies have shown especially pronounced exaggerated natriuresis in subjects with low renin essential hypertension, "10 we included a subgroup in this category as a posi...

Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake

“…In contrast, our experiments demonstrated an enhanced ability to excrete an acute salt load in LSD1-deficient mice. This result is consistent with previous studies in humans, where low renin hypertensives hyperexcreted a salt load in contrast to normotensives or non-modulating hypertensives (a normal renin form of salt-sensitive hypertension) (Cottier et al 1958;Krakoff et al 1970;Luft et al 1977;Rydstedt et al 1986;Hollenberg et al 1986). In this study (data not shown) and previously (Pojoga et al 2011b), renin and aldosterone levels were suppressed in LSD1-deficient mice on HS diet, indicating that activation of the RAS is not a driving force for elevated blood pressure.…”

Atrial natriuretic peptide in non-modulating essential hypertension.

“…In contrast with this hypothesis, the renin response to saline infusion is not completely restored by 3 days of treatment with enalapril, 26 suggesting alternative explanations for the renin behavior. In our opinion, the reduced ANP increase after Ang II infusion could be taken into consideration.…”

“…After blood collection, renal plasma flow was assessed in both hypertensive patients and control subjects according to the method described by Rystedt et al 26 Briefly, at 9 AM, after 1 hour in a supine position, patients had an intravenous catheter installed in the right arm. A control blood sample was obtained, and /j-aminohippurate (PAH) (bolus injection of 8 mg/kg) was infused.…”

Epidemiology of blood pressure and predictors of hypertension.

“…There are, however, examples of bimodally distributed, hypertension-related phenotypes such as modulating and nonmodulating sodium sensitivity. 22 It is also encouraging to note that RFLPs for the renin gene have recently been identified in animal models of hypertension. 23 -24 Thus, RFLPs are among the most promising of the future hypertension predictors, not solely because of their potential for forecasting risk, but also because they can frequently serve as effective entries to more in-depth pathophysiologic studies.…”