Renin suppression by saline is blunted in nonmodulating essential hypertension.

Abstract

SUMMARY We have reported that 50% of subjects with normal renin essential hypertension have both delayed suppression of the renin-angiotensin-aldosterone axis following sodium infusion and a delayed rate of excretion of an acute salt load. In another study we have also described a subset of patients with essential hypertension (called nonmodulators) who have several abnormalities, including a pressor response to salt loading. To evaluate whether the abnormalities described in these different groups of patients actually occur in the same patient, we assessed the renin-angiotensinaldosterone axis response to short-term saline loading in 38 hypertensive patients. Their ability to modulate was determined by their renal vascular response to infused angiotensin II on a high salt diet (200 mEq Na). In response to a 3-hour infusion of saline, 75 mEq/hr, the reduction in plasma renin activity at both 60 and 120 minutes was significantly greater (p<0.008) in patients with normal modulation than in the nonmodulators. Plasma aldosterone levels were also significantly lower (p < 0.001) in those with intact modulation. Thus, nonmodulating essential hypertensive patients have abnormalities in several systems that influence sodium homeostasis, including altered adrenal and renal vascular response to angiotensin II, altered renal blood flow response to salt loading, and a delayed suppression of the renin-angiotensin-aldosterone system with short-term saline infusion. reported that approximately 50% of subjects with normal renin essential hypertension have a delayed suppression of the reninangiotensin-aldosterone axis with saline infusion. These same hypertensive subjects also had a delayed rate of excretion of the salt load compared with normotensive subjects. Recently, we reported that approximately 50% of normal and high renin essential hypertensive subjects fail to increase renal blood flow or enhance renal vascular responsiveness to angiotensin

Atrial natriuretic peptide in non-modulating essential hypertension.

“…Then, an impaired aldosterone response to acute volume depletion was described by Williams et al 2 in a similar subgroup of hypertensive patients. At present, other characteristics of non-modulating hypertension have been described (see References 3 and 4 for review), including an increased blood pressure sensitivity to dietary salt intake 5 and decreased I) renal blood flow response to both angiotensin II (Ang II) and sodium loading, 5 -6 2) aldosterone response to Ang II, 6 3) renin suppression after both Ang IP and saline infusions, 8 and 4) sodium excretion after sodium loading. 9 Because an impaired responsiveness to Ang II of the adrenal gland and kidney seems to determine the hormonal and hemodynamic characteristics of nonmodulators, a tissue refractoriness to Ang II has been suggested as the primum movens of non-modulating hypertension (see References 3 and 4 for review).…”

“…26 as well as a suggested defect in both volume-and sodiumsensitive intrarenai receptors, 8 has been indicated as the primary defect leading to the lack of renin suppression.…”

Non-modulating hypertension. A subset of sodium-sensitive hypertension.

“…First, when subjects are sodium restricted and placed in the upright position, the plasma renin activity and angiotensin II levels tend to be higher and the plasma aldosterone levels tend to be lower in non-modulators; thus, a lower change in aldosterone/change in plasma renin activity ratio results. 16 Second, both angiotensin II 17 and acute sodium chloride infusion 18 have a reduced ability to suppress plasma renin activity in the sodium-restricted non-modulator. Third, plasma dopamine levels are increased in nonmodulators, particularly on a low sodium intake, and…”

“…Decreased renal blood flow response to angiotensin II on high salt diet 14 Decreased renal blood flow response to sodium loading 14 ' 15 Decreased aldosterone response to angiotensin II on low salt diet 14 Renin suppression by angiotensin II on low salt diet 17 Renin suppression by saline on low salt diet 18 Reduced sodium excretion 20 Decreased increments in aldosterone divided by increments in renin in response to posture and sodium restriction 18 Corrected by converting enzyme inhibitors? Elevated sodium-lithium countertransport in red blood cells 21 Increased plasma norepinephrine levels in response to posture and salt restriction Increased plasma dopamine levels 22 References are indicated for the various characteristics.…”

Renal and endocrine response to saline infusion in 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.…”