Augmentation in the kinetic characteristics of phenylephrine- and 5-hydroxytryptamine-induced contractions in the isolated rat aorta following eight weeks of STZ-diabetes

Christ, George J.; Valcic, Mira; Gondré, Marjorie

doi:10.1016/0024-3205(94)00564-8

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…29 Christ et al showed a diabetes related increase in phenylephrine induced contractions of 8-weeks-STZ-rat aorta. 30 The changes to a more contractile state may be explained by an altered cellular Ca 2 distribution. 29,31 Melman et al and Lincoln et al found a reduction of the NA content in nerve ®bers in corpus cavernosum from diabetic men compared to non-diabetics.…”

Section: Discussionmentioning

confidence: 99%

Effects of diabetes on neurotransmission in rat vaginal smooth muscle

et al. 2001

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The aim of this work was to characterize the effect of experimental diabetes on neurotransmission in rat vagina. Female Sprague ± Dawley rats were divided into two groups: non-diabetic controls (NDM, n 38) and diabetics (DM, n 38). DM was produced by intraperitoneal injection of streptozotocin. Eight weeks later the animals were killed, the distal part of the vagina was removed, and smooth muscle strips were prepared for functional organ bath experiments and for measurement of nitric oxide synthase (NOS) activity. In DM preparations, the EC 50 value for noradrenaline (NA) was signi®cantly increased (P`0.05) and the maximal contractile response decreased (P 5 0.001). In preparations precontracted with NA, the NO donor SNAP and calcitonin gene-related peptide (CGRP) caused concentration-dependent relaxations, which were signi®cantly decreased (P`0.001) in the DM group. Electrical stimulation of nerves (EFS) caused frequency-dependent contractions, which were signi®cantly lower in DM than in NDM strips (P`0.001). SNAP and CGRP concentration-dependently inhibited EFS evoked contractions in both NDM and DM preparations. The inhibition was signi®cantly lower (P`0.05) in the DM group. In NDM preparations precontracted with NA, EFS evoked frequency-dependent relaxations; such relaxations were inhibited or reduced in DM. Treatment with the NOS inhibitor, L-NOARG 0.1 mM, abolished relaxations in all preparations or produced contraction in DM preparations. Calcium-dependent NOS activity was not signi®cantly different in the DM and NDM groups. However, the DM animals showed a small but signi®cant increase in calcium-independent NOS-activity (P`0.05). Diabetes interferes with adrenergic-, cholinergic-and NANC-neurotransmitter mechanisms in the smooth muscle of the rat vagina. The changes in the nitrergic neurotransmission are not due to reduction in NOS-activity, but seem to be due to interference with later steps in the L-arginineaNOaguanylate cyclaseacGMP system.

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Section: Discussionmentioning

confidence: 99%

Effects of diabetes on neurotransmission in rat vaginal smooth muscle

et al. 2001

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“…The effects of vasoactive agents on conduit vessels like the aorta (Durante et al 1988;Cameron and Cotter 1992;Christ et al 1994) and the superior mesenteric artery (MacLeod 1985;White and Carrier 1988) have been investigated extensively in diabetic animals (for review : Öztürk et al 1996). The altered vascular reactivity in experimental diabetes has been attributed to endothelial (Durante et al 1988; White and Carrier 1988) and smooth muscle dysfunctions (Öztürk et al 1996), although there is disagreement regarding the involvement of the vascular endothelium.…”

Section: Introductionmentioning

confidence: 99%

Vascular responses of isolated mesenteric resistance and basilar arteries from short- and long-term diabetic rats

Buren

Vleeming

Krutzen

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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Vascular dysfunctions, e.g. alterations in the reactivity of blood vessels to neurotransmitters and hormones, are a well-established complication of diabetes mellitus. Whether these impairments are a consequence of direct postsynaptic deficits and/or indirect presynaptic deficits remains to be determined. To this end, we investigated the influence of the duration of diabetes on relaxation and contraction responses of isolated mesenteric resistance and equally-sized basilar arteries to postsynaptic activation by various vasoactive agents, using streptozotocin-induced diabetic rats and age-matched controls. Relaxation responses to vasodilator agents were studied in KCl-precontracted arteries. The duration of diabetes (4 or 40 weeks) did not affect the vasodilator responses to sodium nitroprusside or salbutamol in either artery. In mesenteric resistance vessels from short-term (4 weeks) and long-term (40 weeks) diabetic rats the vasoconstrictor responses to KCI, serotonin and vasopressin were the same as those in non-diabetic rats; however, the sensitivity (EC50) to noradrenaline was slightly but significantly enhanced after the long-term diabetic state. In contrast to the mesenteric arteries, noradrenaline did not cause contraction in basilar arteries taken from diabetic and control rats. Thus, there appear to be important differences in the reactivity to noradrenaline of the peripheral and cerebral vasculature. The basilar artery from short-term and long-term diabetic rats did not show different responsiveness to vasopressin whereas to serotonin a significant enhanced and decreased sensitivity (EC10 and EC50) was demonstrated in short-term and long-term diabetes, respectively. Our findings indicate that postsynaptic impairments do not play a major role in the alterations of vasoreactivity to vasodilators, noradrenaline or vasopressin seen in experimental diabetes. However, the duration of the diabetic state may have serious consequences for vasoreactivity of basilar arteries to serotonin and, therefore, warrants further investigations.

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“…Taken together, these results with the results of the present study indicate the importance of 5‐HT 2 receptor blockade in the treatment of diabetic nephropathy. Because vascular sensitivity to 5‐HT in diabetic patients has been shown to be enhanced, 1 , 2 our observations suggest that renal hyperreactivity to 5‐HT is more deeply involved in patients with the more profound renal complications. Moreover, the blockade of 5‐HT 2 receptors with sarpogrelate improved the incidence of a cold sensation in the lower extremities.…”

Section: Discussionmentioning

confidence: 72%

“…Therefore, great care is taken to prevent aggravation of diabetic angiopathy. In diabetic patients, the vasoconstrictor response to 5‐hydroxytryptamine (5‐HT) has been suggested to be increased due to 5‐HT 2 receptor hypersensitivity, probably causing vascular dysfunction 1 , 2 . Moreover, in diabetes, enhancement of vasoconstrictor thromboxane (TX)A 2 has been suggested to be involved in the aggravation of diabetic complications 3 –5 .…”

Section: Introductionmentioning

confidence: 99%

THE 5‐HT₂ RECEPTOR ANTAGONIST SARPOGRELATE REDUCES URINARY AND PLASMA LEVELS OF THROMBOXANE A₂ AND URINARY ALBUMIN EXCRETION IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS PATIENTS^†

Ogawa

Takeuchi

Sugimura

et al. 1999

Clin Exp Pharma Physio

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1. Therapeutic effects of a 5-HT2 receptor antagonist sarpogrelate on microalbuminuria and thromboxane (TX)A2 biosynthesis were examined in non-insulin-dependent diabetes mellitus (NIDDM) patients. 2. In protocol I, the ankle-brachial pressure index (API; an indicator of peripheral blood flow) and urinary albumin excretion (UalbV; an indicator of renal function) were determined in 42 NIDDM patients who had been treated with 300 mg/day sarpogrelate for 8 weeks. In an analysis of the results, the NIDDM patients were divided into four groups based on the severity of either vasculopathy or nephropathy as follows: group A, API < 0.9, UalbV > or = 100 mg/day; group B, API < 0.9, UalbV < 100 mg/day; group CAPI > or = 0.9, UalbV > or = 100 mg/day; and group D, API > or = 0.9, UalbV < 100 mg/day. 3. In protocol II, 10 NIDDM patients with UalbV values > 100 mg/day were divided into two groups to further confirm the effect of sarpogrelate on albuminuria: group E, the sarpogrelate treatment group (n = 5); and group F, the no treatment group (n = 5). 4. In protocol I, the incidence of a cold sensation in the lower extremities was reduced from 45.2 to 21.4% following sarpogrelate treatment. In patients with UalbV > or = 100 mg/day (groups A and C), UalbV was significantly decreased independent of API, while it did not change in patients with UalbV < 100 mg/day (groups B and D). Plasma TXB2 levels were significantly decreased following sarpogrelate treatment, whereas plasma 6-keto-prostaglandin F1 alpha levels were not. 5. In protocol II, in the sarpogrelate treatment group (group E), albuminuria was significantly improved and both plasma levels TXB2 and urinary TXB2 excretion were significantly decreased. In contrast, in the untreated group (group F), neither plasma levels TXB2 nor urinary TXB2 excretion was changed. 6. In conclusion, microalbuminuria was improved by treatment with the 5-HT2 receptor antagonist sarpogrelate independent of latent vasculopathy. Blockade of 5-HT2 receptors is suggested to be beneficial for the treatment of nephropathy in NIDDM patients. It is possible that the inhibition of TXA2 biosynthesis is involved in the therapeutic effect of 5-HT2 receptor antagonists.

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Augmentation in the kinetic characteristics of phenylephrine- and 5-hydroxytryptamine-induced contractions in the isolated rat aorta following eight weeks of STZ-diabetes

Cited by 11 publications

References 26 publications

Effects of diabetes on neurotransmission in rat vaginal smooth muscle

Effects of diabetes on neurotransmission in rat vaginal smooth muscle

Vascular responses of isolated mesenteric resistance and basilar arteries from short- and long-term diabetic rats

THE 5‐HT₂ RECEPTOR ANTAGONIST SARPOGRELATE REDUCES URINARY AND PLASMA LEVELS OF THROMBOXANE A₂ AND URINARY ALBUMIN EXCRETION IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS PATIENTS^†

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Augmentation in the kinetic characteristics of phenylephrine- and 5-hydroxytryptamine-induced contractions in the isolated rat aorta following eight weeks of STZ-diabetes

Cited by 11 publications

References 26 publications

Effects of diabetes on neurotransmission in rat vaginal smooth muscle

Effects of diabetes on neurotransmission in rat vaginal smooth muscle

Vascular responses of isolated mesenteric resistance and basilar arteries from short- and long-term diabetic rats

THE 5‐HT2 RECEPTOR ANTAGONIST SARPOGRELATE REDUCES URINARY AND PLASMA LEVELS OF THROMBOXANE A2 AND URINARY ALBUMIN EXCRETION IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS PATIENTS†

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THE 5‐HT₂ RECEPTOR ANTAGONIST SARPOGRELATE REDUCES URINARY AND PLASMA LEVELS OF THROMBOXANE A₂ AND URINARY ALBUMIN EXCRETION IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS PATIENTS^†