Inhibitory Effects of Insulin on Intracellular Calcium and Aggregatory Response of Platelets Are Impaired in Hypertensive Subjects with Insulin Resistance

• Published in: Hypertension Research Vol. 20; no. 3; pp. 225 - 231
• Main Authors: Ishibashi, Ken-ichi, Kageyama, Shigeru, Sakurai, Tatsuya, Murakawa, Yuichi, Aihara, Kazuo, Yokota, Kuninobu, Taniguchi, Ikuo, Hashimoto, Yoshiaki, Fujita, Toshiro, Tajima, Naoko
• Format: Journal Article
• Language: English
• Published: England The Japanese Society of Hypertension 1997
• Subjects: Adult; Blood Glucose - metabolism; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood Pressure - drug effects; calcium; Calcium - blood; glucose clamp; Glucose Clamp Technique; Heart Rate - drug effects; Humans; hypertension; Hypertension - blood; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; insulin resistance; Insulin Resistance - physiology; Male; platelet aggregation; Platelet Aggregation - drug effects; Thrombin - pharmacology; Vasodilator Agents - pharmacology
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1291/hypres.20.225

To determine the effects of insulin on intracellular calcium and platelet aggregatory responses in hypertensive subjects with insulin resistance, we measured insulin sensitivity in terms of glucose disposal rate (GDR) by the hyperinsulinemic euglycemic clamp technique (GC) in 14 non-diabetic untreated hypertensive subjects, and determined basal ([Ca2+]i) and thrombin-stimulated (T-[Ca2+]i) platelet-free calcium concentrations and thrombin-stimulated platelet aggregatory response (AG) before (PRE[Ca2+]i, T-PRE[Ca2+]i, and PRE AG, respectively) and during (POST[Ca2+]i, T-POST[Ca2+]i, and POST AG, respectively) GC. As a control for GC, vehicle (normal saline) was infused on another day. No significant difference was observed between PRE[Ca2+]i and POST[Ca2+]i, T-PRE[Ca2+]i and T-POST[Ca2+]i, or PRE AG and POST AG. GDR inversely correlated with Δ[Ca2+]i (POST[Ca2+]i- PRE[Ca2+]i, r=-0.75, p<0.02), ΔT-[Ca2+]i (T-POST[Ca2+]i-T-PRE[Ca2+]i, r=-0.63, p<0.02) and ΔAG (POST AG-PRE AG, r=-0.67, p<0.01). No significant changes were observed in these variables during vehicle infusion. [Ca2+]i, T-[Ca2+]i, and AG decreased during GC as compared with baseline in hypertensive subjects with normal insulin sensitivity, but were unchanged in those with insulin resistance, suggesting that the vasodilatory and anti-platelet aggregatory effects of insulin are impaired in patients with insulin-resistant hypertension. (Hypertens Res 1997; 20: 225-231)