Prevailing theory holds that abnormally large increases in renal salt retention and cardiac output are early pathophysiologic events mediating initiation of most instances of salt-induced hypertension. This theory has come under increasing scrutiny because it is based on studies that lack measurements of sodium balance and cardiac output obtained during initiation of salt-loading in proper normal controls, i.e., salt-resistant subjects with normal blood pressure. Here we make the case for a “vasodysfunction” theory for initiation of salt-induced hypertension: In response to an increase in salt intake, a subnormal decrease in total peripheral resistance that involves a subnormal decrease in renal vascular resistance, in the absence of abnormally large increases in sodium retention and cardiac output, is the hemodynamic abnormality that usually mediates initiation of salt-induced increases in blood pressure (BP). It is the failure to normally decrease vascular resistance in response to salt loading that enables a normal increase of cardiac output to initiate the salt-induced increase in blood pressure. This theory is based on the results of properly controlled studies which consistently demonstrate that in salt-sensitive subjects, salt-loading initiates increased BP through a hemodynamic mechanism that: 1) does not usually involve early increases in sodium retention and cardiac output greater than those which occur with salt-loading in normal controls, and 2) usually involves an early failure to decrease vascular resistance to the same extent as that observed during salt-loading in normal controls. Multiple mechanisms including disturbances in nitric oxide and sympathetic nervous system activity likely underlie this subnormal vasodilatory response to salt that usually precedes and initiates salt-induced hypertension.

The results suggest an intricate relationship between inflammation and cartilage turnover, which can in turn be influenced by timing after injury and patient factors.

Purpose: The purpose of this study was to investigate the changes in landing biomechanics over a three-year period and its correlation with cartilage degenerative changes in the medial tibiofemoral joint of the knee after anterior cruciate ligament reconstruction (ACLR) using magnetic resonance (MR) T1 ρ mapping. Methods: Thirty-one ACL injured patients underwent magnetic resonance imaging (MRI) of the injured knee prior to ACLR and three years after ACLR as well as biomechanical analysis of a drop-landing task at six months and three years after ACLR. Sixteen healthy individuals were recruited and underwent knee MRI and biomechanical assessment during a drop-landing task. T 1ρ cartilage relaxation times were calculated for the medial femur and tibia. Results: ACLR patients exhibited increased peak vertical ground reaction forces (VGRF), VGRF impulse, peak knee flexion moment (KFM) and KFM impulse from six months to three years (P<0.001, respectively). Although the ACLR knees showed significantly lower peak VGRF and KFM at six months (P<0.001, respectively) when compared to the controls, there were no significant differences at three years. At three years, ACLR patients showed higher T 1ρ values over the medial femur (P<0.001) and tibia (P=0.012) when compared to their preoperative and healthy

The purpose of this proof-of-concept study was to develop three-dimensional patient-specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imaging (MRI) data were used for segmenting the knee geometries, including the cartilage lesions. Based on these geometries, finite element (FE) models were developed. The gait of the patients was obtained using a motion capture system. Musculoskeletal modeling was utilized to calculate knee joint contact and lower extremity muscle forces for the FE models. Finally, a cartilage adaptation algorithm was implemented in both FE models. In the algorithm, it was assumed that excessive maximum shear and deviatoric strains (calculated as the combination of principal strains), and fluid velocity, are responsible for the FCD loss. Changes in the longitudinal T 1ρ and T 2 relaxation times were postulated to be related to changes in the cartilage composition and were compared with the numerical predictions. In patient 1 model, both the excessive fluid velocity and strain caused the FCD loss primarily near the cartilage lesion. T 1ρ and T 2 relaxation times increased during the follow-up in the same location. In contrast, in patient 2 model, only the excessive fluid velocity led to a slight FCD loss near the lesion, where MRI parameters did not show evidence of alterations. Significance: This novel proof-of-concept study suggests mechanisms through which a local FCD loss might occur near cartilage lesions. In order to obtain statistical evidence for these findings, the method should be investigated with a larger cohort of subjects.

Abstract-Normotensive salt sensitivity, a putative precursor of hypertension, might be quite frequent in African Americans (blacks) and less frequent in Caucasian Americans (whites), but only when dietary potassium is deficient and not when maintained well within the normal range. We tested this hypothesis in 41 metabolically controlled studies of 38 healthy normotensive men (24 blacks, 14 whites) who ate a basal diet low in sodium (15 mmol/d) and marginally deficient in potassium (30 mmol/d) for 6 weeks. Throughout the last 4 weeks, NaCl was loaded (250 mmol/d); throughout the last 3, potassium was supplemented (as potassium bicarbonate) to either mid-or high-normal levels, 70 and 120 mmol/d. Salt sensitivity, defined as an increase in mean arterial blood pressure Ն3 mm Hg with salt loading, was deemed "moderate" if increasing Յ10 mm Hg and "severe" if increasing more. When dietary potassium was 30 mmol/d, salt loading induced a mean increase in blood pressure only in blacks (PϽ0.001), and salt sensitivity occurred in most blacks but not whites (79% vs 36% (PϽ0.02). Supplementing potassium only to 70 mmol/d attenuated moderate salt sensitivity similarly in blacks and whites; 120 mmol/d abolished it, attenuated severe salt sensitivity, which occurred in a quarter of affected blacks, and suppressed the frequency and severity of salt sensitivity in blacks to levels similar to those observed in whites. These observations demonstrate that in most normotensive black men but not white men, salt sensitivity occurs when dietary potassium is even marginally deficient but is dose-dependently suppressed when dietary potassium is increased within its normal range. Such suppression might prevent or delay the occurrence of hypertension, particularly in the many blacks, in whom dietary potassium is deficient. (Hypertension. 1999;33:18-23.)