Independent relationships between renal mechanisms and systemic flow, but not resistance to flow in primary hypertension in Africa

Abstract

Whether renal mechanisms of hypertension primarily translate into increases in systemic vascular resistance (SVR) in all populations is uncertain. We determined whether renal mechanisms associate with either increases in SVR (and impedance to flow) or systemic flow in a community of African ancestry.Method: In a South African community sampled across the full adult age range (n ¼ 546), we assessed stroke volume (SV), peak aortic flow (Q), SVR, characteristic impedance (Zc) and total arterial compliance (TAC) from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures. Renal changes were determined from creatinine clearance (glomerular filtration rate, GFR) and fractional Na þ excretion (FeNa þ ) (derived from 24-h urine collections).Results: Independent of confounders (including MAP and pressures generated by the product of Q and Zc), SV (and hence cardiac output) (P < 0.0001) and Q (P < 0.01), but not SVR, Zc or TAC (P ¼ 0.09-0.20) were independently associated with decreases in both GFR (index of nephron number) and FeNa þ . Through an interactive effect (P < 0.0001), the impact of GFR on SV or Q was strongly determined by FeNa þ and vice versa. The relationship between the GFR-FeNa þ interaction and either SV or Q was noted in those above or below 50 years of age, although neither GFR, FeNa þ nor the interaction were independently associated with SVR, Zc or TAC at any age. Conclusion:Across the full adult lifespan, in groups of African ancestry, renal mechanisms of hypertension translate into increases in systemic flow rather than into resistance or impedance to flow.

Marked intrafamilial aggregation and heritability of aortic flow in a community with prevalent volume-dependent hypertension in Africa

“…The main findings of the present study are as follows: In a large (n ¼ 669) community sample in Africa, recently demonstrated to show a striking contribution of age-dependent, renal-related increases in systemic blood flow to PP and SBP in hypertension [6][7][8], we compared the intrafamilial aggregation and heritability of systemic flow to that of the vascular determinants of PP and hence SBP. In this regard, in-line with conventional physiological principles, and the 'Windkessel' model of the systemic circulation, PP in the brachial pulse is determined by the product of flow (Q) and the resistance to flow in a pulsatile system (Z c ) with an additional contribution from arterial compliance.…”

“…However, in the present population, the increases in systemic flow are attributed to an age-related, volume-dependent increase in left ventricular preload (Frank-Starling effect) [6]. The presence of an age-related volume-dependent increase in systemic flow is supported by strong relations of systemic flow with age-related increases in left ventricular end diastolic volume, an age-related reduction in circulating renin concentrations and both age-related and nonagerelated alterations in several indices of renal tubular function [6,8]. In contrast, no relationships between systemic flow and ejection fraction are noted in this population [6].…”

“…Haemodynamic parameters were determined from noninvasive central arterial pressure measurements derived from peripheral pulse wave analysis and the assessment of aortic velocity and diameter in the outflow tract [6][7][8]. After participants had rested for 15 min in the supine position, arterial waveforms at the radial (dominant arm) pulse were recorded by applanation tonometry during an 8 s period using a high-fidelity SPC-301 micromanometer (Millar Instrument, Inc., Houston, Texas, USA) interfaced with a computer employing SphygmoCor, version 9.0 software (AtCor Medical Pty.…”

“…Thus, in contrast, to several populations around the world, in groups of African ancestry living in Africa, increases in systemic flow are as important as the vascular determinants of BP in the pathogenesis of hypertension [6,7]. Although renal mechanisms explain the marked increases in systemic flow but not alternative haemodynamic determinants of BP [8], current antihypertensive therapy, including diuretic therapy has no proven ability to produce sustained decreases in systemic blood flow. Thus, antihypertensive therapy is unlikely to target a dominant haemodynamic mechanism responsible for hypertension in Africa.…”

“…Originating from hot equatorial countries [10], groups of African descent are thought to have evolved to develop hypertension frequently attributed to a genetically predetermined alteration in renal tubular Na þ reabsorption that enhances fluid retention [11,12]. Although possibly improving the chances of survival in fluid losing states, together with an age-related loss of nephrons, this effect is now recognized as accounting for an enhanced systemic flow in primary hypertension in Africa [8]. Thus, genetic as opposed to environmental factors may play a critical role in mediating the dominant haemodynamic determinant of hypertension in Africa, that is renal-related increases in systemic flow [8].…”