Relationship Between Insulin Resistance and Endothelium-Dependent Vascular Relaxation in Patients With Essential Hypertension

Abstract

The mfuslon of L-argmme mduces the productron of mtrtc oxrde and sttmulates the immediate secretron of msuhn To examme the relatronshrp between msulm reststance and endothelmm-dependent vascular relaxatton m patrents with essential hypertension, we evaluated the renal and msulm responses to L-argmme, 500 mg/kg infused mtravenously over 30 mmutes, m 23 patients with mild essenttal hypertensron who were neither obese nor diabetic and m 20 normotenstve control subJects We found no difference between the two groups m blood glucose or msulm m the fasting condrtton The renovascular relaxatron mduced by L-argmme was srgmficantly less m patients with essential hypertension than m normotensrve control subJects The mcrease m plasma cychc GMP in response to L-arginine was lower m hypertensive patients than m normotensive SubJeCtS Although the serum concentrattons of glucose m response to L-argmme were smular m the two groups, the serum msulm response of me essenhal hypertensrves was srgmficantly hrgher than that of the normotensive subJects In all subJects, the peak cychc GMP response to L-argmme was srgmficantly correlated wtth the peak Aglucose/ Amsulm ratto response to L-argmme (r= 69, P< 001) Fmdmgs suggested that an impanment of endothehum-dependent renal vascular relaxation and a reduced sensrtrvtty to msulm are present m patients with essential hypertension A lmk may be present between the abnormahty of the L-argmmelmtrrc oxide/cyclic GMP pathway and msulm resistance m patients with essential hypertension (Hypertension. The vasodilatory effect of msulm is reportedly mediated by the stimulation of the release of NO.26127 If so, there should be a dtrect physiologrcal correlation between msulm resistance and vascular endothehal dysfunction m patients with essential hypertension The mfusion of L-argmme induces the production of NO-cGMP and sttmulates the immediate secretron of msulm. An elevated plasma level of argmme is a particularly potent stimulus for insulin secretion, although the mechanism 1s not completely known 2829 We examined the responses to renal ctrculation and glucose/msulm to infused L-argmme to evaluate the relattonshtp between rnsulrn sensrtrvtty and endothebal function in patients with essential hypertension Subjects MethodsWe studied 23 Japanese mpattents with mild to moderate essential hypertension (16 males and 7 females, mean age 47 -t-3 years) and 20 normotensive control subJects (14 males and 6 females, mean age 4522 years) Hypertension was defined as a systolic or diastolic blood pressure of more than 160 mm Hg or/and 95 mm Hg, determmed m stttmg posmon on at least three different occastons Measurements were obtained m the outpatient clmtc of Hiroshima University School of Medrcme Patients with secondary forms of hypertenston were excluded by the appropriate chmcal and btochemtcal exammatrons None of the pattents had a hrstory of cardiovascular or cerebrovascular disease, drabetes melhtus, hypercholesterolemla, hver dtsease, or renal dtsease Normotenston was defined as a systohc blood ...

Long-Term Oral l-Arginine Administration Improves Peripheral and Hepatic Insulin Sensitivity in Type 2 Diabetic Patients

“…Although in the present study arginine levels were not measured to confirm the effectiveness of L-arginine supplementation, the significant decrease in vascular resistance (18) and the increase in cGMP (19), a second messenger of NO, strongly supports the positive compliance of patient and therapy. It is currently believed that NO interacts with soluble guanylate cyclase, leading to the elevation of cGMP concentrations (19 -21).…”

Differential blood pressure effects of oral glucose and intravenous L-arginine in healthy lean normotensive and obese hypertensive subjects

“…[21][22][23] Interestingly, endo- thelial dysfunction favours vasoconstriction and BP elevations during glucose and insulin infusions. [10][11][12][13][14]23 Endothelial dysfunction has been observed in hypertensives, obese and type-2 diabetics; conditions characterised by the presence of insulin resistance, compensatory hyperinsulinaemia and glucose intolerance. [12][13][14] Consequently, both hyperinsulinaemia and hyperglycaemia may play a role in the hypertension of obesity.…”

“…It is known that endothelial dysfunction potentiates the hypertensive responses to insulin and glucose. [10][11][12][13][14]23 L-arginine, elevated plasma insulin, without significant increases in plasma glucose levels. Infusion of L-arginine was associated with BP lowering.…”

“…[10][11][12][13][14] It is thus possible, that the small increase in glucose and insulin induced by oral glucose in lean normotensives produced a small, but significant BP reduction. In fact, insulin-induces vasodilation in normal subjects [8][9][10][11][12][13][14] and glucose induces minimal BP changes in healthy animals'. 23 The failure to observe BP lowering in obese hypertensives is most likely due to hyperglycaemia and hyperinsulinaemia in the presence of insulin resistance and to possible endothelial dysfunction.…”

“…[1][2][3][4][5][6][7] In healthy subjects, insulin induces vasorelaxation and increases tissue blood flow; 8,9 these effects are diminished or lost in the subjects with endothelial dysfunction and/or insulin resistance. [10][11][12][13] Insulin resistance with compensatory hyperinsulinaemia has been observed in lean hypertensives, obese normotensives and hypertensives and in patients with type 2 diabetes mellitus. 2,[14][15][16][17][18] Infusions of insulin have been shown to increase blood pressure (BP) in rats.…”