Raising lipids acutely reduces baroreflex sensitivity.

Impaired baroreflex sensitivity (BRS) is associated with hypertension and cardiovascular risk. Lipid abnormalities accompanying insulin resistance may impair BRS. To test this, nine obese, dyslipidemic hypertensive and seven healthy normotensive individuals were studied. The BRS was measured during a phenylephrine infusion before and after nonesterified fatty acids (NEFAs) and triglycerides were raised for 1 h with an Intralipid and heparin infusion, ie, acute dyslipidemia. The obese group had higher values than lean controls for several components of the insulin resistance syndrome including blood pressure (BP) and heart rate, as well as fasting insulin, triglycerides, and NEFA. The BRS was lower in obese hypertensive subjects than healthy controls at baseline (P < .0001); BRS declined from 8.3 +/- 0.4 to 5.2 +/- 0.3 (P < .001) in obese hypertensive subjects and from 15.9 +/- 2.2 to 7.5 +/- 0.7 msec/mm Hg (P = .04) in controls with acute dyslipidemia. The reduction in BRS correlated with the rise in NEFAs (r = -0.59, P = .02) but not triglycerides (r = -0.07, P = NS). These observations indicate that elevating NEFAs acutely impairs BRS. The findings suggest that lipid abnormalities in obese hypertensives may contribute to elevated BP and increased cardiovascular events by impairing BRS.

Hemodynamic effects of nicotinic acid infusion in normotensive and hypertensive subjects.

Nicotonic acid (NA) infusions are associated with peripheral vasodilation from the generation of vascular prostaglandins with minimal effects on blood pressure (BP) in normotensive subjects. We studied the effects of a NA infusion in 10 hypertensive and 11 normotensive individuals to further characterize systemic hemodynamic responses to NA using pulse waveform analysis. Blood pressure, stroke volume, cardiac output, total peripheral resistance, large and small artery elasticity were determined before and after a 1-h NA infusion. In the normotensives, systolic, diastolic, mean BP, and pulse pressure were not affected by NA. In contrast, the hypertensive subjects experienced a decrease in mean BP from 105 +/- 2 mm Hg to 100 +/- 3 mm Hg (P <.01) accompanied by significant decreases in systolic, diastolic, and pulse pressures. The differential BP response occurred despite comparable increases in heart rate (11% to 13%, P

Insulin's actions on plasma free fatty acids are normal in patients with stage 2 to 3 chronic kidney disease.

Resistance to insulin's action to suppress plasma nonesterified fatty acids (NEFA) is implicated in the hypertension and hyperlipidemia characterizing the metabolic syndrome. It is unknown whether insulin resistance to NEFA suppression is linked to hypertension and dyslipidemia in patients with mild chronic kidney disease (CKD). Eight patients with nonnephrotic, nondiabetic stage 2 to 3 CKD (I(125)-iothalamate clearances of 56 +/- 6 mL/min) and 7 hypertensive (HT) and 8 normotensive (NT) subjects with normal kidney function matched for age, gender, race, and percent body fat were studied. Plasma oleate, linoleate, palmitate, and stearate were measured during a 2-stage euglycemic hyperinsulinemic clamp procedure. Insulin suppressed plasma linoleate and oleate similarly in CKD (81%, 84%) and NT subjects (84%, 85%, respectively; P = NS) but less in HT patients (67%, 70%, P < .05 vs. CKD and NT). Likewise, the sum of NEFA were equally suppressed in the CKD and NT groups (P = NS) but not in HT subjects (P < .01 both vs. CKD and NT). Percent body fat correlated highly with NEFA suppression in the CKD and NT groups but not in HT subjects. Impairment of insulin's antilipolytic actions is not involved in the early pathogenesis of dyslipidemia and hypertension in patients with mild to moderated renal dysfunction.