Abnormal Renin Short Feedback Loop in Essential Hypertension Is Reversible with Converting Enzyme Inhibition

LeBoff, Meryl S.; Dluhy, Robert G.; Hollenberg, Norman K.; Moore, Thomas J.; Koletsky, Richard J.; Williams, Gordon H.

doi:10.1172/jci110622

Cited by 12 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Captopril has been shown repeatedly to cause a reactive rise in renin release and an increase in PRA, 24 demonstrated here to vary with basal PRA. The very low PRA values measured after enalkiren administration replicate previous reports.…”

Section: Discussionsupporting

confidence: 55%

Responses to converting enzyme and renin inhibition. Role of angiotensin II in humans.

et al. 1994

View full text Add to dashboard Cite

We compared the renal vascular responses to angiotensin converting enzyme inhibition and renin inhibition to assess the influence of angiotensin II (Ang II). We examined the renal and endocrine responses to the renin inhibitor enalkiren, to captopril, and to placebo in nine healthy and nine hypertensive men on a 10-mmol sodium diet. Ang II was infused to assess effects of the agents on renal and adrenal responsiveness to Ang II. Plasma Ang II concentration was suppressed similarly with enalkiren and captopril -an identical level of blockade was achieved. Although renal plasma flow was stable during placebo, a substantial rise was seen with both enalkiren (+133±26 mL/min per 1.73 m 2

show abstract

Section: Discussionsupporting

confidence: 55%

Responses to converting enzyme and renin inhibition. Role of angiotensin II in humans.

et al. 1994

View full text Add to dashboard Cite

show abstract

“…PRA increased after administration of ARB during insulin infusion and during sham insulin infusion, consistent with interruption of "short feedback" by AngII (29). The rise in renin tended to be greater during insulin infusion, consistent with insulin-induced activation of the RAS.…”

Section: Discussionmentioning

confidence: 53%

Insulin Induces Renal Vasodilation, Increases Plasma Renin Activity, and Sensitizes the Renal Vasculature to Angiotensin Receptor Blockade in Healthy Subjects

Perlstein

Gerhard‐Herman

Hollenberg

et al. 2007

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

T he success of blockade of the renin-angiotensin system (RAS) in improving the natural history of diabetic nephropathy (1) suggests that hyperglycemia-mediated activation of the RAS has an important role in the pathogenesis of diabetic kidney disease. It is interesting that renal structural features that are characteristic of diabetic nephropathy precede the appearance of overt diabetes, indicating that renal injury begins in the prediabetic phase (2). A cardinal feature of the prediabetic phase is insulin resistance and consequent hyperinsulinemia (3), raising the possibility that hyperinsulinemia itself may activate mechanisms of renal injury.A growing body of experimental evidence suggests that insulin activates the RAS (4 -8). Acute hyperinsulinemia increases plasma renin activity and plasma level of the potent renal vasoconstrictor angiotensin II (9 -11). In seeming contradiction, acute hyperinsulinemia also induces nitric oxide (NO)-dependent renal vasodilation (12). The effect of insulin to stimulate both the RAS and NO in the renal vasculature is of particular interest given the key role of RAS/NO balance in renal physiology and pathophysiology (13) and the accumulating evidence that insulin resistance and hyperinsulinemia are risk factors for chronic kidney disease (14 -16).We sought to examine the relationship between insulin-induced renal vasodilation and insulin-induced activation of the RAS. We performed the hyperinsulinemic euglycemic clamp technique in healthy volunteers and compared the renal vasodilator response to angiotensin receptor blockade (ARB) during hyperinsulinemia with the response on a control study day. Renal vascular responsiveness to interruption of the RAS is increased in states of activation of the RAS, such as low sodium compared with high sodium balance (17), and has been used to demonstrate hyperglycemia-induced activation of the RAS (18 -20). We examined the relationships between insulin-induced renal vasodilation, insulin-induced renin secretion, and insulininduced sensitization of the renal vasculature to ARB. Our findings suggest that insulin simultaneously stimulates vasoconstrictor and vasodilator mechanisms in the human kidney and that insulin-induced RAS activation modulates the renal vasodilator effect of insulin. Materials and Methods ParticipantsFifteen healthy volunteers (nine men and six women) participated in this study. Exclusion criteria were the presence of any chronic medical or psychiatric disorder, smoking, heavy alcohol use, overweight (body

show abstract

“…6 ' ' • a Converting enzyme inhibition was shown in an earlier study to correct the abnormality in ANG II-mediated suppression of renin release. 22 That observation also raised the intriguing possibility that inappropriate intrarenal concentrations of ANG II contributed to the sluggish response of renin release to increments in plasma ANG II concentration created by an infusion.…”

mentioning

confidence: 99%

Renal and endocrine response to saline infusion in essential hypertension.

Rydstedt¹,

Williams²,

Hollenberg³

1986

Hypertension

View full text Add to dashboard Cite

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...

show abstract

Abnormal Renin Short Feedback Loop in Essential Hypertension Is Reversible with Converting Enzyme Inhibition

Cited by 12 publications

References 19 publications

Responses to converting enzyme and renin inhibition. Role of angiotensin II in humans.

Responses to converting enzyme and renin inhibition. Role of angiotensin II in humans.

Insulin Induces Renal Vasodilation, Increases Plasma Renin Activity, and Sensitizes the Renal Vasculature to Angiotensin Receptor Blockade in Healthy Subjects

Renal and endocrine response to saline infusion in essential hypertension.

Contact Info

Product

Resources

About