Obesity is an emerging concern in the US and Western Countries. The effect of rising body mass index (BMI) on blood pressure and hemodynamics in normotensive populations is not known. We examined blood pressure (BP, oscillometric), heart rate (HR) and hemodynamic parameters (cardiac output CO, systemic vascular resistance SVR, by thoracic bioimpedance) in 737 normal subjects evaluated as renal donors by gender and BMI. Mean age was 42±1 years (range 18-75), with 305 males, 432 females. Treated hypertensives were excluded. BP and heart rate rose progressively with rising BMI. Cardiac output increased with BMI accompanied by reduced postural change in impedance. SVR fell slightly at high BMI. Indexing values for body surface area eliminated or reversed the rise in cardiac output with BMI. Indexed values suggested a rise in SVRI with reduced stroke volume and CO as the explanation for higher BP with higher BMI. Taken together, absolute hemodynamic measures demonstrate volume expansion with obesity leading to elevated BP. SVR fails to fall adequately to balance higher cardiac outputs accounting for higher BP with increased BMI. Indexed values reverse this impression and artifactually suggest systemic vasoconstriction. These findings raise concern that indexing to body size may distort vascular patterns particularly at high BMI. (See Table) Mean ± SEM TFI: thoracic impedance, ΔTFI: impedance change with posture. p < 0.05 vs BMI < 25 p < 0.05 vs BMI 25–29.9 p < 0.05 vs BMI 30–34.9. Mean ± SEM TFI: thoracic impedance, ΔTFI: impedance change with posture. p < 0.05 vs BMI < 25 p < 0.05 vs BMI 25–29.9 p < 0.05 vs BMI 30–34.9.

Hypertension prevalence increases with advancing age, accompanied by increasing arterial stiffness. Whether comparable vascular changes occur in normotensive individuals with aging is not known. We examined blood pressure (BP, oscillometric), heart rate (HR) and hemodynamic parameters (stroke volume SV, cardiac output CO, systemic vascular resistance SVR, by thoracic bioimpedance) by age decade in 640 normal subjects evaluated as renal donors. Those with hypertension (>140/90 mmHg or antihypertensive medication), renovascular or renal disease were excluded. Mean age was 41± 1 years (range 18-72), with 256 males, 384 females. Systolic and diastolic BP rose with age. CO declined, mediated by lower SV while HR was unchanged. SVR increased progressively with age. Trends were similar when hemodynamic measurements were indexed to body surface area. Absolute impedance rose with age as did impedance change with posture. While BP and CO were lower and HR and SVR higher in women compared to men, hemodynamic changes with age occurred in parallel. Once indexed to BSA, CO and SVR measures did not differ by gender even though BP was lower in women. Our results indicate a prevailing age-related rise in vascular tone mediates higher BP with advancing age in association with normal to low cardiopulmonary volume. As CO falls, BP rise is mediated by accentuated systemic vasoconstriction. This may result in declining perfusion to multiple vascular beds including the kidney, accounting for the decline in glomerular filtration rate seen with aging via reduced renal blood flow. See Table 1. Mean ± SEM, p < 0.05 vs age 18–30 p < 0.05 vs age 31–40 p < 0.05 vs age 41–50. TFI: supine thoracic impedance, ΔTFI: impedance change with posture. Mean ± SEM, p < 0.05 vs age 18–30 p < 0.05 vs age 31–40 p < 0.05 vs age 41–50. TFI: supine thoracic impedance, ΔTFI: impedance change with posture.

Calcineurin inhibitors are a mainstay of transplant immunosuppression and commonly induce hypertension. They are highly lipid soluble and penetrate vascular smooth muscle cell membranes readily. Changes in vascular tone are universally observed during administration of these agents, particularly within the kidney, leading to diminished glomerular filtration and enhanced sodium retention. Disturbances of endothelial function are prevalent in many tissues, including stimulation of endothelin and impaired nitric oxide synthesis. Multiple additional pathways produce increased vasoconstriction, leading to an increase in arterial pressure. Clinical manifestations include disturbances in circadian blood pressure patterns, left ventricular hypertrophy, and acceleration of atherosclerotic and renal injury. Rapid increases in pressure occasionally produce accelerated hypertension and microangiopathic tissue damage. Principles of therapy require recognition of hazards of changing arterial pressures during calcineurin use and preferential use of vasodilating drugs, particularly dihydropyridine calcium channel blocking agents. Attention must be paid to interactions between antihypertensive agents and calcineurin inhibitor blood levels.