It has been proposed that several neurohumoral factors may be involved in the genesis of vascular structural changes (remodeling or hypertrophy) frequently observed in essential hypertension. Therefore, in this study we investigated vascular structural alterations of subcutaneous small resistance arteries in patients with secondary forms of hypertension. The study included 70 participants: 11 with pheochromocytoma, 13 with primary aldosteronism, and 17 with renovascular hypertension; 13 normotensive subjects and 16 patients with essential hypertension served as controls. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph, and media-lumen ratio, media thickness, remodeling index, and growth index were evaluated. Endothelial function was evaluated according to the dose-response curve to acetylcholine. In patients with either primary aldosteronism or renovascular hypertension, a marked increase in media-lumen ratio was observed, whereas in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in patients with essential hypertension. The increase in media-lumen ratio in patients with essential hypertension and with pheochromocytoma was mainly due to vascular remodeling (remodeling index, 93% to 94%), whereas in patients with renovascular hypertension, there was vascular growth (remodeling index, 70%; growth index, 53%). Patients with primary aldosteronism had an intermediate pattern compared with the other two forms of secondary hypertension. An evident impairment of endothelial function was observed in all four hypertensive groups. In conclusion, the renin-angiotensin-aldosterone system seems to be more powerful than the adrenergic system in inducing vascular growth.

ACE DD genotype may be considered a risk factor for the development of common carotid intima-media thickening in our study population.

Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.

Abstract-The amI of our study was to evaluate the relatlonshlps between endothehal function, small resistance artery structure, and blood pressure m patients with primary or secondary hypertension Sixty subJects were included m the study 9 patients with pheochromocytoma, 10 with primary aldosteromsm, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotenslve subjects who served as controls Chmc and 24-hour ambulatory blood pressure (ABPM) were evaluated All subjects were submitted to a biopsy of subcutaneous fat Small resistance arteries were dissected and mounted on a mlcromyograph and the media/lumen ratio was calculated A dose-response curve to acetylcholme was performed at cumulative concentrations from lo-" to 10m5 mol/L The vasodllator response to acetylcholme was slmllarly Impaired m the four groups of hypertensive patients (ANOVA P< 05 versus normotenslve controls), without any significant difference among them In subcutaneous small arteries of patients with either primary aldosteromsm or renovascular hypertension, a marked increase m media lumen ratio was observed, whrle m patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed m essential hypertension No slgmficant correlation between media-lumen ratio or chmc blood pressure and maximum acetylcholme-induced vasodllatatlon was observed On the contrary, a significant, albelt not very close, correlation between ABPM values and maximum acetylchohne-induced vasodllatatlon was observed (r=34, P< 05 with 24-hour systolic blood pressure, r=O 36, P< 05 with 24-hour dlastohc blood pressure) In conclusion, endothehal dysfunction seems to be mdependent from the degree of vascular structural alterations and from the etiology of hypertension, and it 1s probably more linked to the hemodynamlc load (Hypertension. 1998;31[part 2]:335-341.)Key Words: acetylcholme n endothelmm w EDRF n nitric oxide I vascular resistance w hypertrophy n secondary hypertension E ndothehal cells are known to have important regulatory effects on the cardiovascular system through the release of vasodllator and vasoconstnctor mediators " In small resistance arteries, endothehum seems to have a key role m the imbalance between vasoconstnctlon and vasodllatatlon ' An impairment of the endothehal function, as evaluated by the vasodllator response to acetylcholme, has been detected m human small resistance arteries both m essentla13" and m secondary hypertension ' 5Structural abnormahtles of the media of the resistance vessels are common accompamments of chronic hypertension, and they play an Important role m the mcrease of vascular reststance, and, therefore, m the maintenance of high blood pressure values " We have previously demonstrated that the extent and the charactenstlcs of structural alterations observed m subcutaneous small resistance arteries of patients with primary or secondary forms of hypertension are not umform 4 In particular, m patients with either primary aldosteromsm or renovascular hypertension,...

Coumarins and structurally related compounds have been recently shown to present anti-human immunodeficiency virus, type 1 (HIV-1) activity. Among them, the dietary furanocoumarin imperatorin is present in citrus fruits, in culinary herbs, and in some medicinal plants. In this study we report that imperatorin inhibits either vesicular stomatitis virus-pseudotyped or gp160-enveloped recombinant HIV-1 infection in several T cell lines and in HeLa cells. These recombinant viruses express luciferase as a marker of viral replication. Imperatorin did not inhibit the reverse transcription nor the integration steps in the viral cell cycle. Using several 5 long terminal repeat-HIV-1 constructs where critical response elements were either deleted or mutated, we found that the transcription factor Sp1 is critical for the inhibitory activity of imperatorin induced by both phorbol 12-myristate 13-acetate and HIV-1 Tat. Moreover in transient transfections imperatorin specifically inhibited phorbol 12-myristate 13-acetate-induced transcriptional activity of the Gal4-Sp1 fusion protein. Since Sp1 is also implicated in cell cycle progression we further studied the effect of imperatorin on cyclin D1 gene transcription and protein expression and in HeLa cell cycle progression. We found that imperatorin strongly inhibited cyclin D1 expression and arrested the cells at the G 1 phase of the cell cycle. These results highlight the potential of Sp1 transcription factor as a target for natural anti-HIV-1 compounds such as furanocoumarins that might have a potential therapeutic role in the management of AIDS.

The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dysfunction, in human and experimental hypertension is still unclear. Moreover, the interrelationships between structural and functional vascular alterations are presently under debate. The aim of this study was to assess the arteriolar wall thickness and left ventricular mass as well as the vascular response to norepinephrine and acetylcholine in spontaneously hypertensive rats (SHR), before and after the development of hypertension, as compared to age-matched normotensive Wistar-Kyoto rats (WKY). Seventeen SHR (4 to 12 weeks old) and 17 WKY were included in the study. Blood pressure was measured noninvasively. After killing the animals, relative left ventricular mass (RLVM) was calculated, and mesenteric arcades were dissected and mounted on a micromyograph. Functional and structural characteristics of the vessels were measured: media thickness (MT), media/lumen ratio (M/L), and wall tension in response to norepinephrine and acetylcholine. At 4 weeks of age, no difference in blood pressure and RLVM between SHR and WKY was detected, but MT and M/L of mesenteric small resistance arteries were significantly greater in SHR. An increased response to norepinephrine was observed in terms of wall tension, but not of active media stress at the two higher norepinephrine concentrations. No difference in the dose-response curve to acetylcholine between SHR and WKY was observed. At 8 and 12 weeks of age systolic blood pressure was significantly higher in SHR; RLVM, MT, and M/L were also higher at this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract-We evaluated the effects on cardiovascular structure of the angiotensin-converting enzyme (ACE) inhibitor enalapril and of the angiotensin II receptor blocker losartan, administered either at hypotensive or nonhypotensive dosage in spontaneously hypertensive rats (SHR). SHR were treated from ages 4 to 12 weeks with low-dose (1 mg) losartan. Untreated WKY and SHR were also studied. Rats were killed at 13 weeks of age, and the heart was weighed. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of media thickness and lumen diameter. In fixed arteries, cell volume, number of cells per segment length, and number of cell layers were measured using the unbiased "disector" method. Systolic blood pressure was significantly reduced by the high doses of both drugs, but the hypotensive effect was greater with enalapril than with losartan (PϽ0.05). In the high-dose enalapril and losartan groups, there were similar reductions in relative left ventricular mass, media/lumen ratio, and number of cell layers of resistance arteries; however, there were no differences in the cell volume or number of cells per segment length of resistance arteries. Low-dose enalapril did not affect systolic blood pressure or any of the structural parameters. The results show that the hypotensive effects of both losartan and enalapril were associated with outward remodeling of resistance arteries at the cellular level. The effect of losartan on resistance artery structure was equal to that of enalapril, despite the smaller hypotensive effect. (Hypertension. 1998;32:305-310.) Key Words: losartan Ⅲ enalapril Ⅲ hypertrophy Ⅲ angiotensin-converting enzyme inhibitors Ⅲ angiotensin II Ⅲ vascular resistance T he renin-angiotensin-aldosterone system seems to play a key role in the development of cardiac and vascular hypertrophy that is usually observed in both humans and animal models of genetic or experimental hypertension.

The aim was to determine, in a cross-sectional study, the relation between structural alterations in the heart and carotid arteries, and blood pressure (BP) changes from day to night time, measured by ambulatory BP (ABP). In 225 untreated subjects (