Arterial wall viscosity (AWV) is a potential source of energy dissipation in circulation. That arteries, which are known to be markedly viscous in vitro, have lower viscosity in vivo has been suggested but not demonstrated under similar pressure conditions. Endothelium, which may modulate AWV through smooth muscle tone, could contribute to the low level of viscosity in vivo. Our objectives were first to compare AWV of the rat abdominal aorta, in vivo and in vitro, with similar pulse-pressure waves, and second, to determine whether endothelial function influences AWV in vivo and in vitro. The diameter of the abdominal aorta and distending pressure were measured in vivo and in vitro with a high-resolution echotracking system and a micromanometer, respectively. AWV was calculated as the area of the pressure-volume curve hysteresis. After in vivo examination, the arterial segments were isolated in vitro and submitted to resynthesized pressure waves identical to those recorded in vivo. Deendothelialization was performed in vivo by balloon rubbing; then arteries were examined either in vivo or in vitro. AWV was markedly lower in vivo than in vitro (6.6 +/- 0.7 versus 22.7 +/- 3.7 J.m-1.10(-5), respectively; P < .001). After deendothelialization, a sustained 40% increased AWV was observed during a 15-minute follow-up (P < .01). In vitro, deendothelialized arteries have a 64% higher AWV than segments with endothelium (P < .01). Our results indicate that the physiological effective viscosity, measured in vivo in intact animals, is threefold lower than the intrinsic viscosity of the arterial wall, measured in vitro. Endothelium removal determines a sustained increase in AWV, either in vivo or in vitro. These results suggest that active mechanisms compensate for intrinsic viscosity under physiological conditions. One of these energy-saving mechanisms might be dependent on normal endothelial function.

Hypertensive men have a higher prevalence of erectile dysfunction (ED) than the general population. Experimental evidence of ED in hypertensive animals is scarce. This study evaluates the erectile function of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) in vivo by the increase in intracavernosal pressure after electrical stimulation of the cavernous nerve (CN) and by isometric tension studies on corporal strips. Frequency-dependent erectile responses to CN stimulations were reduced in SHR. Phenylephrine induced lower corporal contractions in SHR although pD2 values were similar to WKY. Endothelium-dependent relaxations to ACh were impaired significantly in SHR, and indomethacin improved these relaxations in both WKY and SHR, the latter thus reaching values similar to WKY. Corporal relaxations to sodium nitroprusside were enhanced in SHR. Thus a dysfunctional alpha-adrenergic contraction of the corporal smooth muscle, an increased cyclooxygenase-dependent constrictor tone, and/or a defect in endothelium-dependent reactivity are associated with the altered erectile mechanisms in SHR. Drugs targeting endothelial dysfunction may delay the occurrence of ED as a complication of hypertension.

Abstract-The reactivity of old hypertensive rat aortas has not been investigated in relation to each phenotype of the blood pressure curve, mean arterial pressure (MAP), and pulse pressure (PP). Aortic reactivities from 3-to 78-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were studied with the use of organ chambers and invasive blood pressure, carotid diameter, and histomorphometry. MAP and PP were elevated in SHR, but at 78 weeks, a selective increase of PP without further MAP increase was observed for the same carotid diameter as WKY. Aortic relaxation in response to carbamylcholine decreased similarly with age in both strains. With (ϩ) or without (Ϫ) endothelium (E), maximal developed tension (MDT) under KCl increased linearly with age in SHR, proportionally to wall thickness and MAP increase. Under norepinephrine (NE), MDT of E Ϫ aortas from SHR and controls increased with age and reached plateaus at 12 weeks, whereas MDT of E ϩ aortas from SHR increased linearly with age. Because the NE-induced MDT was higher for E Ϫ than E ϩ , the difference estimated endothelial function. This difference reached plateaus from 12 to 78 weeks in WKY but was abolished beyond 12 weeks in SHR, a finding also observed under NO-synthase inhibition. In old hypertensive rats, (1) increased KCl reactivity is endothelium independent but influenced by the MAP-dependent aortic hypertrophy with resulting increased vascular smooth muscle reactivity, whereas (2) increased NE reactivity is endothelium dependent in association with increased PP, altered endothelial function, and extracellular matrix, with resulting enhanced intrinsic arterial stiffness. (Hypertension. 2001;37:313-321.)

N-(2-Indanyl)-glycinamide hydrochloride (CHF3381) is a novel low-affinity, noncompetitive N-methyl-D-aspartate receptor antagonist. The current study compared the antinociceptive effects of CHF3381 with those of gabapentin and memantine in in vitro and in vivo models of pain. In isolated rat spinal cord, CHF3381 and memantine, but not gabapentin, produced similar inhibition of the wind-up phenomenon. CHF3381 suppressed the maintenance of carrageenan-induced thermal and mechanical hyperalgesia in the rat with a minimum significantly effective dose (MED) of 30 mg/kg p.o. Memantine produced a partial reversal of both thermal and mechanical hyperalgesia (MED ϭ 10 and 15 mg/kg i.p., respectively). Gabapentin reversed mechanical hyperalgesia (MED ϭ 10 mg/kg s.c.), but did not affect thermal hyperalgesia. In the mouse formalin test, CHF3381 and memantine preferentially inhibited the late phase (MED ϭ 30 and 20 mg/kg i.p., respectively); gabapentin inhibited only the late phase (MED ϭ 30 mg/kg s.c.). Unlike morphine, CHF3381 chronic administration was not accompanied by the development of tolerance in the formalin test. Furthermore, morphine tolerance did not cross-generalize to CHF3381. In rats with a sciatic nerve injury, CHF3381 relieved both cold and mechanical allodynia (MED ϭ 100 mg/kg p.o.). In contrast, memantine was inactive. Gabapentin blocked cold allodynia (MED ϭ 30 mg/kg s.c.), but had marginal effects on mechanical allodynia. In diabetic neuropathy, CHF3381 reversed mechanical hyperalgesia (MED ϭ 50 mg/kg p.o.). Memantine (15 mg/kg i.p.) produced an antinociceptive effect, whereas gabapentin (100 mg/kg p.o.) had no significant effect. Thus, CHF3381 may be useful for the therapy of peripheral painful neuropathies.

Taken together, data on the mechanical and reactive properties of radial and internal mammary arteries show why the radial artery displayed a higher potential for spasm than the internal mammary artery and why the use of Ca2+ channel blocker can decrease the incidence of occlusion and spasm.

Abstract-In rats, removal of the carotid arterial or abdominal aortic endothelium results in an acute increase of diameter and compliance. In humans, acute local administration of a specific NO synthase inhibitor increases radial artery compliance but not the diameter. The purpose of this review is to determine whether in spontaneously hypertensive rats (SHR), a cause-and-effect relationship may be observed between endothelial function and arterial stiffness with possible consequences on pulse pressure (PP) control. The study is based on a comparative time-dependent analysis of the following in young and old SHR: aortic blood pressure measurements and reactivity, ultrasonographic arterial stiffness assessment, aortic histomorphometry and staining, and molecular biology with evaluation of endothelium function. In young SHR, aortic mean blood pressure and PP increase proportionally, whereas isobaric arterial stiffness is unchanged or poorly modified. The endothelial NO response to norepinephrine is normal or upregulated as a response to predominant vasoconstrictive influences. In contrast, in old SHR, PP and mean blood pressure change disproportionately with age, together with an enhanced isobaric arterial stiffness. The endothelial NO response to norepinephrine is abolished, in association with endothelium-dependent heightened norepinephrine reactivity and enhanced accumulation of vessel extracellular matrix. In this latter case, exogenous NO acutely and selectively lowers the increased PP. Thus, during SHR aging, a negative feedback may be observed between NO bioactivity and PP through changes in arterial structure and function. Whether this alteration contributes to the development of systolic hypertension in old populations remains to be determined. Key Words: rats, inbred SHR Ⅲ arteries Ⅲ endothelium Ⅲ nitric oxide F or many years, studies of spontaneous hypertension in rats focused on the presence of sympathetic hyperactivity and the mechanisms by which this alteration contributes to changing the mean blood pressure (MBP) and the structure and function of arterioles. 1,2 Subsequently, the role of the vascular endothelium was principally deduced from the investigation of NO-norepinephrine (NE) interactions. 3 Nowadays, hypertension is mainly considered as a cardiovascular risk factor, leading to more attention being focused on the structure and function of hypertensive large arteries, which greatly influence the development of complications in hypertensive vascular disease. 4 It has been widely reported that the conduit arteries of spontaneously hypertensive rats (SHR) are stiffer than those of the corresponding normotensive control rats. 4,5 In addition to blood pressure level, it seems likely that intrinsic modifications of the arterial wall might contribute to the increased stiffness. 4 Because stiffness is influenced by arterial structure and function, changes in vasomotor tone, possibly of endothelial origin, might promote the alterations of the mechanical properties of the SHR conduit arteries.The purpo...

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Under NO synthase inhibition, the vasoactive properties of Japanese and Lyon aorta differ in the presence of a cyclo-oxygenase blocker but not endothelin blockers. These results indicate that the aorta vasorelaxant tone is associated to prostanoid regulation in Lyon but not in Japanese rats. This observation appears dependent on the genetic and/or environmental background linked to the origin and not the presence of hypertension.