Evidence for increased media thickness, increased neuronal amine uptake, and depressed excitation--contraction coupling in isolated resistance vessels from essential hypertensives.

Abstract

The functional and morphologic characteristics of isolated subcutaneous resistance vessels (about 170 fitn i.d.) from 15 untreated subjects with essential hypertension and 15 matched controls were examined. The vessels from the hypertensives had a 29% increase in the media-thickness-to-lumendiameter ratio. The maximal force development to noradrenaline (NA) expressed as active pressure (an estimate of the pressure the vessels could have contracted against in vivo) was 30 % higher in vessels from the hypertensives, while active media stress (force per square unit of smooth muscle) and sensitivity to NA was not significantly different. Increased active pressure, as well as unaltered active media stress and sensitivity, was seen for vasopressin, serotonin, angiotensin II, and K + . There was, however, an enhanced leftward shift of the NA sensitivity with cocaine (an inhibitor of the neuronal amine pump) in vessels from the hypertensives [pD 2 ( + cocaine) and pD 2 ( -cocaine) were 0.185 ± 0.053 and 0.040 ± 0.044, hypertensives and normotensives, respectively, p < 0.05] suggesting an abnormality of presynaptic function in essential hypertension. Furthermore, the calcium sensitivity was depressed (pD 2 was 4.197 ± 0.050 and 4.381 ± 0.068, hypertensives and normotensives, respectively, p < 0.05), and the rate of relaxation was faster (p < 0.05) in vessels from hypertensives, suggesting that excitation-contraction coupling might be depressed. The results suggest that the increased pressor response in essential hypertension can, to a large extent, be explained by altered vascular structure, while smooth muscle function is either unchanged or possibly depressed.

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“…2 Small arteries 65 to 230 m were dissected from the tissue and carefully cleaned under a dissecting microscope. Isolated vessels were then transferred to an arteriographic bath chamber (Living Systems Instruments) 6 and cannulated as described previously.…”

“…1 However, studies in type 2D are fraught with difficulty, given the recognized associations with hypertension and dyslipidemia, both of which are known to influence small-artery structure and function. 2,3 Recently, Rizzoni et al 4 reported that small arteries of patients with type 2D have an increased media thickness to lumen diameter ratio compared with vessels from control subjects: This appeared to be due to a combination of remodeling and hypertrophy. A similar structural change was observed in patients with type 2D and hypertension (type 2DϩH), which contrasted with the eutrophic remodeling reported in patients with essential hypertension (EH).…”

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“…10,11 Small arteries, with an estimated diameter of 100 to 300 m, were dissected from the biopsy specimen and 2 artery segments were mounted as ring preparations in a myograph. 10 Lumen diameter and media thickness were measured in a standardized way as previously described. 10 …”

“…10 Lumen diameter and media thickness were measured in a standardized way as previously described. 10 …”

“…The presence of left ventricular hypertrophy may contribute, 6,7 but structural remodeling of myocardial resistance arteries also seems important. 5 It is well established from hemodynamic measurements in the forearm 8,9 and in vitro studies of isolated small arteries 10,11 that the peripheral resistance vasculature is morphologically altered in essential hypertension. Whether myocardial and peripheral vascular morphology are affected similarly in hypertension remains to be confirmed, but coronary flow reserve has been negatively correlated with the media-to-lumen ratio of subcutaneous small arteries.…”