Seventeen male untreated mild essential hypertensive patients aged 41 ±2 years agreed to participate in a double-blind randomized trial to test the effects of antihypertensive treatment on the structure and function of subcutaneous resistance arteries. Patients were treated with either 50 to 100 mg/d atenolol or 2.5 to 5 mg/d cilazapril. Blood pressure before treatment was 148±6/99±1 and 147±2/99±1 mm Hg, respectively. At 1 year of treatment blood pressure was 131±4/85±2 and 132±2/87±1 mm Hg, respectively. Resistance arteries (200 to 400 /xm lumen diameter) dissected from subcutaneous gluteal biopsies obtained before treatment and at 1 year showed that the media-lumen ratio of arteries from patients treated with cilazapril was reduced to 6.31±0.21% from 7.54±0.31% before treatment (/><.05), still slightly but significantly larger (P<.05) than the media-lumen ratio of resistance arteries of normotensive control subjects (5.15±0.30%). In contrast, in arteries from patients treated with atenolol there was no significant change with treatment (7.97±0.60% before and 8.07±0.45% after 1 year of treatment). Active wall tension responses to endothelin-1 were blunted in hypertensive patients and normalized in the cilazapril-treated patients. Depressed active media stress responses to norepinephrine, arginine vasopressin, and endothelin-1 were accordingly normalized in the patients receiving cilazapril as the media width became thinner but were unchanged in those taking atenolol. These results suggest that treatment for 1 year with the converting enzyme inhibitor cilazapril corrects in part the structural and functional abnormalities present in subcutaneous resistance arteries of patients with mild essential hypertension. {Hypertension. 1994^3:83-91.)Key Words • angiotensin converting enzyme inhibitors • adrenergic beta receptor blockers • hypertrophy • blood vessels • hypertension, essential N ormalization of elevated blood pressure in hypertensive patients has been clearly shown to improve survival and decrease the incidence of stroke and renal and heart failure. 15 However, most clinical trials of antihypertensive treatment have failed to show significant beneficial effects on myocardial ischemia, although meta-analyses have indeed allowed benefit to be demonstrated, albeit to a lesser degree than on the incidence of stroke. 67 The reasons for this relative lack of success have been a matter of discussion but remain unclear. One possible explanation could be that altered vascular structure in hypertensive patients is not normalized by antihypertensive treatment. Persistent abnormalities in blood vessels, particularly in coronary arteries and arterioles, may play a role in this outcome.Alteration of large blood vessels in hypertensive patients has been clearly documented and is mainly associated with atherosclerosis.8 However, the increased peripheral resistance that characterizes high blood pressure in animals and humans is above all the consequence of alterations in the smaller arteries and arterioles, called...

Mechanical properties of arteries are altered in some rat models of hypertension, and this may influence peripheral resistance and blood pressure as well as some of the complications of hypertension. It has usually been assumed that arterial wall stiffness is increased in hypertension, although recent studies suggest that this may not necessarily be the case in large arteries. We determined whether the mechanics of human resistance arteries are altered in hypertension. Subcutaneous resistance arteries (lumen diameter<300 microm) were isolated from hypertensive and normotensive subjects of similar ages (46+/-3 and 43+/-4 years, respectively). Vessels were mounted in a pressurized myograph, deactivated, and exposed to intraluminal pressures ranging from 3 to 140 mm Hg. At each pressure, lumen and media dimensions were measured. Media-to-lumen ratio and media width were greater in hypertensive vessels, reducing wall stress (P<0.01), whereas media cross section was similar in vessels from both groups. Isobaric elastic modulus (which is influenced by vessel geometry and by wall component stiffness) was lower in hypertensive vessels (P<0. 01). Stiffness of wall components (slope of incremental elastic modulus versus stress, which is geometry-independent) was significantly lower in hypertensive vessels (8.2+/-0.7) versus normotensive vessels (11.0+/-1.0, P<0.05), whereas distensibility was unchanged. Electron microscopic analysis of the media of the small arteries showed a greater collagen to elastin ratio (P<0.05) in the media of vessels from hypertensive patients. In conclusion, the stiffness of wall components (slope of elastic modulus versus stress) is not increased but is in fact decreased in subcutaneous resistance arteries from patients with mild essential hypertension. Reduced stiffness of resistance arteries from hypertensive patients does not appear to relate to changes in volume density of extracellular matrix components but may be the result of changes in extracellular matrix architecture or cell-matrix attachment, which remains to be established.

Epigenomic modifications are instrumental for transcriptional regulation, but comprehensive reference epigenomes remain unexplored in rice. Here, we develop an enhanced chromatin immunoprecipitation (eChIP) approach for plants, and generate genome-wide profiling of five histone modifications and RNA polymerase II occupancy with it. By integrating chromatin accessibility, DNA methylation, and transcriptome datasets, we construct comprehensive epigenome landscapes across various tissues in 20 representative rice varieties. Approximately 81.8% of rice genomes are annotated with different epigenomic properties. Refinement of promoter regions using open chromatin and H3K4me3-marked regions provides insight into transcriptional regulation. We identify extensive enhancer-like promoters with potential enhancer function on transcriptional regulation through chromatin interactions. Active and repressive histone modifications and the predicted enhancers vary largely across tissues, whereas inactive chromatin states are relatively stable. Together, these datasets constitute a valuable resource for functional element annotation in rice and indicate the central role of epigenomic information in understanding transcriptional regulation.

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