Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats

Abstract

Chromium picolinate [Cr(pic)(3)] is a nutritional supplement widely promoted to exert beneficial metabolic effects in patients with type 2 diabetes/impaired glucose tolerance. Frequent comorbidities in these individuals include systemic hypertension, abnormal vascular function and ischemic heart disease, but information on the effects of the supplement on these aspects is sparse. Utilizing male spontaneously hypertensive rats (SHR), we examined the potential impact of Cr(pic)(3) on blood pressure, vascular reactivity and myocardial ischemia-reperfusion injury (IRI). Dietary Cr(pic)(3) supplementation (as 10 mg chromium/kg diet for six weeks) did not affect blood pressure of the SHR. Also, neither norepinephrine (NE) and potassium chloride (KCl)-induced contractility nor sodium nitroprusside (SNP)-induced relaxation of aortic smooth muscle from the SHR was altered by Cr(pic)(3) treatment. However, Cr(pic)(3) augmented endothelium-dependent relaxation of aortas, produced by acetylcholine (ACh), and this effect was abolished by N-nitro-L-arginine methyl ester (L-NAME), suggesting induction of nitric oxide (NO) production/release. Treatment with Cr(pic)(3) did not affect baseline coronary flow rate and rate-pressure-product (RPP) or infarct size following regional IRI. Nonetheless, Cr(pic)(3) treatment was associated with improved coronary flow and recovery of myocardial contractility and relaxation following ischemia-reperfusion insult. In conclusion, dietary Cr(pic)(3) treatment of SHR alters neither blood pressure nor vascular smooth muscle reactivity but causes enhancement of endothelium-dependent vasorelaxation associated with NO production/release. Additionally, while the treatment does not affect infarct size, it improves functional recovery of the viable portion of the myocardium following IRI.

Figure 1

Effect of dietary chromium picolinate [(Cr(pic)3] supplementation on mean arterial pressure (MAP), systolic blood pressure (SAP) and diastolic blood pressure (DBP) of spontaneously hypertensive rats (SHR). Animals were treated with (Cr(pic)3-enriched diet containing 10 mg/kg chromium for a period of 3 weeks (panel A) and 6 weeks (panel B) starting at 6 weeks of age; control animals were given standard rat diet. Each bar represents mean ± SEM values from 6 rats/group.

Figure 2

Contractile responses of endothelium-denuded aortas from animal groups described in Figure 1 to norepinephrine (NE) (panel A) and potassium chloride (KCl) (panel B). Each point represents the mean ± SEM of data from 9–15 aortic rings obtained from 6 rats/group.

Figure 3

Panel A shows relaxant responses of endothelium-denuded aortas from animal groups described in Figure 1 to sodium nitroprusside (SNP). Each point represents the mean ± SEM of data from 6 rats/group. Panel B shows relaxant responses of endothelium-intact aortas from animal groups described in Figure 1 to acetylcholine (Ach) in the absence and presence of N-nitro-L-arginine methyl ester (L-NAME). Each point represents the mean ± SEM of data from 6–16 aortic rings obtained from 6 rats/group. * p <0.05 with respect to corresponding control values in the absence of L-NAME.

Figure 4

Line graphs showing coronary flow rate (normalized to ventricular weight (vW); panel A) and bar graphs show rate-pressure-product (RPP, an index of cardiac work; panel B) in animal groups as described in Figure 1. In panel A, Time 0 values represent baseline coronary flow rate. Each value represents the mean ± SEM of data from 6 rats/group. * p<0.05 compared to the untreated SHR at the same time point.

Figure 5

Bar graphs showing indices of myocardial contractility (maximum + dP/dt; panel A) and relaxation (maximum – dP/dt; panel B) expressed as percent of baseline values at the end of ischemia and reperfusion for animal groups as described in Figure 1. Also shown is infarct size, expressed as percent of area at risk, for Cr(pic)3-treated and control SHR (panel C). Each value represents the mean ± SEM of data from 6 rats/group. * p<0.05 compared to the untreated SHR. ^# p<0.05 compared to their ischemic values.