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C Aalkjaer

Publications and source records attributed to C Aalkjaer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of acidosis on tension and [Ca2+]i in rat cerebral arteries: is there a role for membrane potential?

The cellular mechanism responsible for the reduction of tension in cerebral small arteries to acidosis is not known. In this study the role of smooth muscle intracellular Ca2+ concentration ([Ca2+]i) and membrane potential for the relaxation to acidosis was investigated in isolated rat cerebral small arteries. Isometric force was measured simultaneously with [Ca2+]i (fura 2) or with membrane potential (intracellular microelectrodes), and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution. Both hypercapnic and normocapnic acidosis were associated with a reduction of intracellular pH [measured with 2',7'-bis-(carboxyethyl)-5 (and -6)-carboxyfluorescein], caused relaxation, and reduced [Ca2+]i. However, whereas hypercapnic acidosis caused hyperpolarization, normocapnic acidosis was associated with depolarization. It is concluded that a reduction of [Ca2+]i is in part responsible for the direct effect of the acidosis on the vascular smooth muscle both during normo- and hypercapnia. The mechanism responsible for the reduction of [Ca2+]i differs between the hypercapnic and normocapnic acidosis, being partly explained by hyperpolarization during hypercapnic acidosis, whereas it is seen despite depolarization during normocapnic acidosis.

Acidosis↗
PubMed1997

Tissue expression of components of the renin-angiotensin system in experimental post-infarction heart failure in rats: effects of heart failure and angiotensin-converting enzyme inhibitor treatment.

1. It has been suggested that local tissue renin-angiotensin systems may be activated in heart failure and that effects on such systems may, at least partially, explain the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in this syndrome. To investigate these hypotheses, we examined expression of renin-angiotensin system components in several tissues in a rodent model of post-myocardial infarction (MI) heart failure, and analysed whether such expression is modified by ACE inhibitor treatment. 2. Four groups of rats (n = 8 - 12 per group) were studied 30 days after surgery: (A) sham-operated rats with no treatment, (B) rats with post-MI heart failure induced by ligation of the left coronary artery, (C) sham-operated rats treated with the ACE inhibitor perindopril (1.5 mg day-1 kg-1), and (D) rats as per B, but treated with perindopril. Expression of renin, angiotensinogen, ACE and angiotensin subtype 1 receptor was assessed by quantification of their respective mRNAs by Northern blotting. 3. Renal renin mRNA increased 2-fold in animals with MI (group B) compared with controls (group A) (P < 0.05) and between 50 and 100-fold after ACE inhibitor treatment (P < 0.001). No change in renin gene expression was found in any extra-renal site either following MI or after ACE inhibitor treatment. Hepatic angiotensinogen mRNA level was similar in all groups, but kidney angiotensinogen mRNA level was increased 1.6-fold (P < 0.01) in the groups receiving perindopril. ACE mRNA level in the lung was not affected by ACE inhibitor treatment but decreased by 50% following MI (groups B and D, P < 0.01). This was associated with a similar (50%, P < 0.01) fall in lung ACE activity and was correlated with the severity of heart failure. Angiotensin subtype 1 receptor mRNA level was not affected in any tissue by either MI or ACE inhibitor treatment. 4. We did not find a systematic activation of tissue renin-angiotensin systems, as assessed by steady-state mRNA levels of key components of the system in experimental post-MI heart failure, or a major effect of ACE inhibitor treatment on expression of these components. However, we observed tissue-specific changes in expression of selected components of the renin-angiotensin system in the kidney and the lung in post-MI heart failure and after ACE inhibitor treatment, which may be of relevance to the pathophysiology of the syndrome and the effects of ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

pH and smooth muscle.

In this paper, the control of vascular smooth muscle intracellular pH (pHi) and the mechanisms of importance for the vasodilation to acidosis are reviewed. The three transport pathways of importance for the control of pHi are a sodium-coupled bicarbonate transport, a Na,H-exchanger and a Cl,HCO3- exchange. While the two latter pathways are present in all smooth muscle cells studied, the sodium-coupled bicarbonate transport may be present in two forms which are either coupled to chloride efflux or are independent of chloride. The chloride-independent pathway seems electroneutral, indicating a 1:1 stoichiometry. All three transporters can be activated by vasoactive hormones and the second messengers involved are under intense investigation. With respect to the mechanisms involved in the vasodilation to acidosis, there seems to be a nitric oxide-dependent pathway as well as a direct effect of acidosis on the smooth muscle cells. In some preparations, prostanoids may also be involved. The direct vasodilator effect of acidosis is probably mediated through reduction of extracellular pH and the acidosis is associated with a reduction of the intracellular calcium concentration, which could explain the reduction of smooth muscle tone.

Acidosis↗
PubMed1997

Vasorelaxation in isolated bone arteries. Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, and bradykinin studied in pigs.

We assessed the effects of vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and bradykinin in arteries (diameter approximately 230 microns) isolated from cancellous bone from pigs. Arterial segments (2 mm long) were mounted on a myograph for measurement of isometric force development. After submaximal precontraction with norepinephrine, VIP (10(-10)-10(-7) M), CGRP (10(-11)-10(-7) M), SP (10(-6) M), and bradykinin (10(-11)-10(-6) M) were added. 44 arterial segments (23 pigs) were investigated. VIP-, CGRP-, and bradykinin induced a concentration-dependent vasorelaxation, while SP mediated a transient relaxation. After mechanical removal of the endothelium, the effects of SP and bradykinin were completely abolished, while the relaxation to CGRP was still pronounced. This indicates that the effects of SP and bradykinin are mediated by the endothelium, while CGRP mainly mediates relaxation by a direct effect on vascular smooth muscle cells. The relaxations to CGRP and bradykinin were still significant after inhibition of nitric oxide synthase with 10(-4) M N omega-nitro-L-arginine (L-NNA) and inhibition of prostaglandin synthesis with 10(-5) M indomethacin, indicating the existence of an alternative vasorelaxing pathway. Our findings support the theory of a vasoregulatory role of neuropeptides in bone.

Animals↗
PubMed1996

Method for assessment of vascular reactivity in bone: in vitro studies on resistance arteries isolated from porcine cancellous bone.

Knowledge about vascular regulation in bone is central to the understanding of both normal and pathological bone physiology. This article describes a new method for direct assessment of the reactivity of bone blood vessels. Resistance arteries (diameter approximately 250 microns) were isolated from epiphyseal cancellous bone (porcine femoral condyle). Arterial segments (2 mm long) were mounted as ring preparations on a myograph, and isometric force development was measured continuously. Fifty-nine vessels from 31 pigs were investigated. The active force development was maximal at 0.9 x L100 in nine of 12 investigated arteries (L100 corresponds to the circumference the vessel would have if relaxed and exposed to a luminal pressure of 100 mm Hg [13.3 kPa]). In all subsequent experiments, the vessels were stretched to 0.9 x L100. Noradrenaline (2 x 10(-8) to 10(-5) M) induced a concentration-dependent vasoconstriction; mean maximal tension development was 3.69 N/m. This force development would enable the arteries to contract against a pressure of more than 22 kPa (165 mm Hg), indicating preserved function of the media smooth muscle. Response to acetylcholine (10(-7) to 10(-5) M) was observed in only two of 12 arteries. Bradykinin (10(-11) to 10(-6) M) induced a concentration-dependent and reproducible relaxation in all vessels; the relaxation was endothelium-dependent, since no effect of bradykinin was detected after mechanical removal of the endothelium. Sodium nitroprusside (10(-4) M) induced a reproducible and endothelium-independent vasorelaxation. The results demonstrate preserved function of both smooth muscle and endothelium in this preparation. The model allows pharmacological investigations of bone arteries under well defined conditions and enables studies on focal bone lesions and human bone tissue.

Animals↗
PubMed1996

The effect of oophorectomy on mechanical properties of rabbit cerebral and coronary isolated small arteries.

OBJECTIVE: Our purpose was to study the effect of oophorectomy on the passive and active mechanical characteristics of rabbit small cerebral and small coronary arteries. STUDY DESIGN: Ring preparations of small cerebral and small coronary arteries from rabbits that had undergone oophorectomy and sham operation were mounted on myographs 6 weeks after operation. Experiments were performed as follows. (1) concentration-response relations for vasopressin (10(-11) to 10(-7) mol/L), U46619 (10(-10) to 10(-6) mol/L), 5-hydroxytryptamine (10(-7) to 10(-5) mol/L), and endothelin (10(-13) to 10(-7) mol/L); (2) relaxing effects of acetylcholine (10(-8) to 10(-4) mol/L); (3) length-tension relations after addition of high potassium (124 mmol/L), vasopressin (10(-7) mol/L), and a mixture composed of potassium (124 mmol/L), vasopressin (10(-7) mol/L), and prostaglandin F 2 alpha (10(-5) mol/L); (4) calculation of vessel morphologic features and determination of hydroxyproline as a measure of collagen content. RESULTS: Oophorectomy did not influence basal tone, relaxant effects of acetylcholine, vessel morphologic features, elastic characteristics, or hydroxyproline content of the vessels. However, in cerebral arteries at a normalized lumen diameter, oophorectomy induced a marked increase in the force development after stimulation with agonists but not after depolarization with high potassium. The reason for this was a leftward shift in the active length-tension curves (vasopressin activation). In coronary arteries none of these changes were seen after oophorectomy. CONCLUSION: These data demonstrate that withdrawal of ovarian hormones changes the position of the active length-tension curve for pharmacomechanical but not electromechanical coupling of small cerebral arteries without interference with the elastic characteristics of these vessels.

Acetylcholine↗
PubMed1996

Increase by lysophosphatidylcholines of smooth muscle Ca2+ sensitivity in alpha-toxin-permeabilized small mesenteric artery from the rat.

1. Pharmacological characterization of different lysophosphatidylcholines was performed based on their effect on the Ca2+ sensitivity of contraction in alpha-toxin-permeabilized rat mesenteric arteries. Furthermore, the effect of noradrenaline on [3H]-myristate-labelled lysophosphatidylcholine levels was assessed, to investigate whether lysophosphatidylcholines could be second messengers. 2. Palmitoyl or myristoyl L-alpha-lysophosphatidylcholine increased the sensitivity to Ca2+, whereas lysophosphatidylcholines containing other fatty acids had less or no effect. 3. L-alpha-phosphatidylcholine, L-alpha-glycerophosphorylcholine, palmitic acid, myristic acid and choline, potential metabolites of lysophosphatidylcholines, did not affect contractions. 4. Noradrenaline (GTP was required) and GTP gamma S increased the sensitivity to Ca2+, and GDP-beta-S inhibited the effect of noradrenaline. Lysophosphatidylcholines, however, had no requirement for GTP and caused sensitization in the presence of GDP-beta-S. 5. Calphostin C, a relatively specific protein kinase C inhibitor, did not affect contraction induced by Ca2+, but abolished the sensitizing effect of lysophosphatidylcholine. 6. Noradrenaline caused no measurable changes in the levels of [3H]-myristate-labelled phosphatidylcholine and lysophosphatidylcholine at 30 s and 5 min stimulation. 7. These results suggest that lysophosphatidylcholines can increase Ca2+ sensitivity through a G-protein-independent, but a protein kinase C-dependent mechanism. However, the role for lysophosphatidylcholines as messengers causing Ca2+ sensitization during stimulation with noradrenaline remains uncertain because no increase in [3H]-myristate labelled lysophosphatidylcholine could be measured during noradrenaline stimulation.

Animals↗
PubMed1996

Some pharmacological and elastic characteristics of isolated subcutaneous small arteries from patients with essential hypertension.

OBJECTIVE: To investigate the elastic characteristics of the wall of isolated subcutaneous resistance arteries from patients with essential hypertension, the response of the vessels to endothelium-dependent and -independent vasodilators and the dependence on calcium. METHODS: Subcutaneous resistance arteries were isolated from 16 patients with never-treated essential hypertension and from 16 normotensive controls matched for age and sex. The vessels were mounted in a myograph for isometric force development. The passive elastic characteristics were determined and then the response to acetylcholine, nitroprusside, felodipine, caffeine and calcium (in the presence of noradrenaline and prazosin or yohimbine) were determined. RESULTS: Young's elastic modulus as a function of wall stress was similar in the two groups of vessels. The relaxation of vessels from hypertensive and normotensive in response to acetylcholine, nitroprusside and felodipine was also similar. However, the response to caffeine was increased in vessels from the hypertensive patients, although the relationship between the dependence on the effect of calcium on the behaviour of arteries from hypertensives and controls was similar in the presence of prazosin and yohimbine. CONCLUSIONS: The altered morphology of subcutaneous resistance arteries from hypertensives is not caused by a change in the elastic characteristics of the wall material. The data support our previous observation of abnormal calcium handling in vessels from hypertensives, although they do not support the hypothesis that a generalized abnormality in endothelium-dependent or endothelium-independent relaxation is of importance in essential hypertension.

Acetylcholine↗
PubMed1995

Regression of media-to-lumen ratio of human subcutaneous arteries and left ventricular hypertrophy during treatment with an angiotensin-converting enzyme inhibitor-based regimen in hypertensive patients.

A total of 25 patients with newly diagnosed or poorly controlled essential hypertension were randomly selected from a larger group referred to hospital. Treatment was initiated with perindopril (4-8 mg orally). If normotension was not achieved, isradipine (5-10 mg orally) was added and, if necessary, hydralazine was added. Before treatment and at the end of a 9-month period of normotension (diastolic blood pressure < or = 90 mm Hg), 24-hour blood pressure and echocardiographic measurements were performed and resistance artery structure was determined. A total of 20 age- and sex-matched normotensives were used as controls. During antihypertensive treatment, mean blood pressure was reduced from 128 +/- 11 to 103 +/- 6 mm Hg. Left ventricular mass was reduced from 300 +/- 76 to 198 +/- 54 g. The media:lumen ratio of the resistance arteries decreased from 9.8 +/- 2.6% to 7.8 +/- 1.9%; control subjects exhibited a media:lumen ratio of the same magnitude (7.9 +/- 2.0%). Results indicate that a perindopril-based regimen is extremely efficient in normalizing resistance artery and cardiac ventricular structures within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension still remains to be demonstrated.

Analysis of Variance↗
PubMed1995

Effect of hypoxia on force, intracellular pH and Ca2+ concentration in rat cerebral and mesenteric small arteries.

1. The effect of severe hypoxia on force, intracellular Ca2+ concentration ([Ca2+]i) and pHi was studied in isolated small arteries from rat brain and rat mesenterium. The arteries were mounted for isometric force recording while [Ca2+]i was measured with fura-2 or pHi was measured with bis-carboxyethylcarboxyfluorescein (BCECF). 2. Hypoxia reduced the force development in response to arginine vasopressin (AVP) while [Ca2+]i was unchanged or only slightly reduced. Inhibition of acid extrusion by omission of sodium caused no force development in mesenteric arteries, but the fall in pHi was enhanced during hypoxia. In cerebral arteries, hypoxia reduced the force development associated with omission of sodium, and the fall in pHi was less than during normoxic conditions. When acid extrusion was intact, pHi was not affected by hypoxia and the changes in pHi during activation with AVP were similar during hypoxia and in the control situation. 3. Although a decrease in smooth muscle [Ca2+]i may be partly responsible for the reduced force development during hypoxia, [Ca2+]i-independent mechanism(s) may play an even more important role. Furthermore, although hypoxia and force development are associated with enhanced acid production, acid extrusion maintains pHi near the control level and it is unlikely that a decrease in smooth muscle pHi plays any role in the reduced force development during hypoxia.

Animals↗
PubMed1995

The relation between peripheral vascular structure, left ventricular hypertrophy, and ambulatory blood pressure in essential hypertension.

The relations between left ventricular mass (LVM), peripheral resistance artery structure, and ambulatory BP were studied in 83 patients with previously untreated or poorly regulated essential hypertension and 20 healthy controls of similar age and sex. LVM was assessed by echocardiography. Signs of left ventricular hypertrophy (LVH) were present in 67 (81%) of the patients and in none of the controls. Peripheral resistance arteries were isolated from surgical gluteal skin biopsies and mounted in a Mulvany-Halpern isometric small vessel myograph, and their media:lumen ratio, media thickness, and media cross-sectional area were determined under standardized conditions. Mean (+/- SD) ambulatory BP was 122 +/- 9 mm Hg among patients and 96 +/- 8 mm Hg among controls (P < .001). LVM was 327 +/- 99 g among patients and 197 +/- 37 g among controls (P < .001). Media thickness of resistance arteries was 21.0 +/- 4.2 microns among hypertensives and 16.2 +/- 2.6 microns among controls (P < .001). The media:lumen ratio of arteries from patients was 10.2 +/- 2.6% v 7.9 +/- 2.0% in arteries of similar internal diameter from controls (P < .01). Both LVM index (LVMI) and media/lumen ratio correlated significantly with BP. There was significant correlation between media:lumen ratio and LVMI among hypertensive patients (r = 0.45, P < .001), but if patients were subdivided according to the presence of LVH this correlation was found only among patients with LVH (r = 0.60 P< .001) and not among patient without LVH nor controls. Multiple regression analyses of age, body surface area, media/lumen ratio, and BP on LVM or LVMI revealed independent contributions of media/lumen ratio and BP. Age had no influence in the models. Similar results were obtained when casual BP was replaced with ambulatory BP in these analyses. No correlation was found between LVMI and media cross-sectional area. A minor subset of patients with complete absence of nocturnal BP drop had particularly great LVM and media:lumen ratio. The study suggests that cardiac and arteriolar tissue undergo parallel structural remodeling in essential hypertension.

Adult↗
PubMed1995

The regulation of pH in resistance arteries from spontaneously hypertensive and Wistar-Kyoto rats: the effect of bicarbonate.

OBJECTIVE: To assess intracellular pH regulation in the presence of bicarbonate in resistance arteries from spontaneously hypertensive rats and Wistar-Kyoto (WKY) rats. METHODS: Intracellular pH was determined in isolated resistance arteries from male adults SHR and WKY rats with the pH-sensitive fluorescent dye bis-carboxyethyl carboxyfluorescein, while the arteries were mounted in a myograph for simultaneous measurements of force. The arteries were acid-loaded using the ammonium chloride technique and the recovery from the acidosis was determined in resting arteries and in arteries activated with 50 mmol/l potassium or arginine vasopressin. This protocol was performed in the presence and in the absence of bicarbonate. RESULTS: In the absence of bicarbonate the intracellular pH was higher in resting arteries from SHR than in those from WKY rats, whereas during activation no significant difference was found. In the presence of bicarbonate no difference in intracellular pH between arteries from SHR and WKY rats could be found. The addition and washout of 15 mmol/l ammonium chloride were associated with large force transients in activated arteries both from SHR and from WKY rats. The proton recovery rate at intracellular pH 6.85 in the absence of bicarbonate was higher in activated arteries from SHR than in those from WKY rats, whereas in resting arteries no significant difference was found. In the presence of bicarbonate no significant difference between SHR and WKY rat arteries was found. CONCLUSION: In the presence of bicarbonate a possible abnormality of the sodium-hydrogen exchange in resistance arteries from SHR is not manifested, because regulation of intracellular pH by bicarbonate-dependent mechanisms can compensate for such an abnormality.

Animals↗
PubMed1995

Effects of tyrosine kinase inhibitors on the contractility of rat mesenteric resistance arteries.

1. A pharmacological characterization of tyrosine kinase inhibitors (TKI) belonging to two distinct groups (competitors at the ATP-binding site and the substrate-binding site, respectively) was performed, based on their effects on the contractility of rat mesenteric arteries. 2. Both the ATP-site competitors (genistein and its inactive analogue, daidzein) and the substrate-site competitors (tyrphostins A-23, A-47 and the inactive analogue, A-1) reversibly inhibited noradrenaline (NA, (10 microM)) and KCl (125 mM) induced contractions, concentration-dependently. Genistein was slightly but significantly more potent than daidzein; the tyrphostins were all less potent than genistein, and there were no significant differences between the individual potencies. The tyrosine kinase substrate-site inhibitor bis-tyrphostin had no inhibitory effect. 3. Genistein, daidzein, A-23 and A-47 each suppressed the contraction induced by Ca2+ (1 microM) in alpha-toxin permeabilized arteries. A-1 and bis-tyrphostin had little or no effect on contraction of the permeabilized arteries. 4. Genistein was significantly more potent than daidzein with respect to inhibition of the contraction induced by 200 nM Ca2+ in the presence of NA (100 microM) and GTP (3 microM). The effect of A-23, A-47, A-1 and bis-tyrphostin was similar in permeabilized arteries activated with Ca2+ (200 nM) + NA (100 microM) + GTP (3 microM) and permeabilized arteries activated with 1 microM Ca2+. 5. Genistein (30 microM) reduced the fura-2 measured intracellular calcium activity ([Ca2+]j) in arteries stimulated with NA but had no effect on [Ca2+]i in arteries stimulated with KCl (125 mM).6. The potent effect of the TKIs in this study is consistent with a role for tyrosine kinases in the mechanisms which regulate both cytoplasmic Ca2+ levels and the effect of Ca2+ on the contractile apparatus in smooth muscle cells in resistance arteries. However, the results must be interpreted cautiously because the enzyme inhibitors may have a poor specificity in intact tissues and because the presumed inactive analogues had potent effects.

Animals↗
PubMed1995

Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension.

In a double-blind randomized trial, the effects of treatment with an angiotensin-converting enzyme (ACE) inhibitor (perindopril) and a beta-blocker (atenolol) on small artery structure were compared in previously untreated essential hypertensive patients. Subjects (diastolic blood pressure > or = 100 and < or = 120 mm Hg) were randomly assigned to treatment for 12 months with either perindopril (n = 13, 4 to 8 mg/d) or atenolol (n = 12, 50 to 100 mg/d); the dosage was adjusted upward and in some cases combined (n = 5, perindopril; n = 2, atenolol) with thiazide diuretic to achieve target blood pressure (diastolic blood pressure below 90 mm Hg). Before and at the end of treatment, gluteal biopsies were taken under local anesthetic; from these biopsies, two small arteries were dissected and mounted on a myograph for morphometry. The reduction in blood pressure with atenolol (drop in mean blood pressure 28.4 +/- 1.8 mm Hg) was greater than with perindopril (20.6 +/- 1.8 mm Hg, P < .05). Perindopril treatment caused an increase in small artery diameter (231 +/- 14 to 274 +/- 13 microns, P < .05) and a reduction in the ratio of media thickness to lumen diameter (7.94 +/- 0.65% to 5.96 +/- 0.42%, P < .05), whereas atenolol had no effect (246 +/- 14 to 231 +/- 13 microns and 7.14 +/- 0.47% to 6.79 +/- 0.45%, respectively). The change in small artery morphology caused by perindopril was not accompanied by any change in media cross-sectional area, suggesting that the change was due to "remodeling."(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Role of extracellular and intracellular acidosis for hypercapnia-induced inhibition of tension of isolated rat cerebral arteries.

The importance of smooth muscle cell pHi and pHo for the hypercapnic vasodilation of rat cerebral arteries was evaluated in vitro. Vessel segments were mounted in a myograph for isometric tension recording; pHi was measured by loading the smooth muscle cells with the fluorescent dye BCECF, and pHo was measured with a glass electrode. In all studies, Ca(2+)-dependent basal tension (in the absence of any agonist) and tension in the presence of arginine vasopressin were investigated. Control solution was physiological saline bubbled with 5% CO2 and containing 25 mmol/L HCO3- (pH 7.45 to 7.50). Induction of hypercapnic acidosis (10% CO2) or normocapnic acidosis (15 mmol/L HCO3-) caused significant inhibition of smooth muscle tension, and both conditions reduced pHi as well as pHo. N-Nitro-L-arginine significantly inhibited the relaxation to hypercapnic acidosis but had no significant effect on relaxation to normocapnic acidosis. Predominant extracellular acidosis, induced by reducing [HCO3-] from 25 to 9 mmol/L and CO2 from 5% to 2.5%, also caused inhibition of tension in steady state. By contrast, predominant intracellular acidosis, induced by increasing [HCO3-] from 25 to 65 mmol/L and CO2 from 5% to 15%, induced a small increase of basal tension and a small decrease of tension in the presence of arginine vasopressin. The responses to predominant intracellular or extracellular acidosis were qualitatively similar in the presence and absence of endothelium and in the presence and absence of N-nitro-L-arginine. It is concluded that the extracellular acidosis and not smooth muscle intracellular acidosis is responsible for the relaxation to hypercapnic acidosis.

Acidosis↗
PubMed1995

Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril.

Untreated essential hypertension is associated with left ventricular hypertrophy (LVH) and structural changes in resistance vessels. The aim of this study was to establish the effect of perindopril based antihypertensive therapy on media thickness to lumen diameter (media:lumen) ratio of peripheral resistance vessels and left ventricular mass in essential hypertension. Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were treated with perindopril. Insufficient treatment response (DBP > 90 mmHg) led to addition of isradipine, and hydralazine was used as a tertiary drug if necessary. Gluteal subcutaneous biopsies were taken surgically at baseline and after 9 months of successful treatment. Two small resistance arteries were isolated and mounted in a small vessel myograph, and media:lumen ratio (%) was measured under standardized conditions. Left ventricular mass was determined by echocardiography. Mean (SD) media:lumen ratio decreased from 9.8 (2.6) % to 7.8 (1.9) % (p < 0.05), while left ventricular mass decreased from 299 (75) g to 199 (53) g (p < 0.001). Correlation was found between changes in left ventricular mass index and media:lumen ratio (r = 0.62, p < 0.01). It is concluded that a perindopril based regimen efficiently normalizes resistance artery structure and left ventricular hypertrophy in essential hypertension within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension remains to be investigated.

Adult↗
PubMed1995

Morphology of isolated small arteries from patients with essential hypertension.

In this paper the morphological results obtained with isolated subcutaneous resistance arteries from patients with essential hypertension are reviewed. There is good agreement from these studies that the lumen diameter is decreased and the media thickness to lumen diameter ratio increased in patients with essential hypertension, which is consistent with data obtained from in vivo measurements of these variables using plethysmographic methods. On the other hand there is little or no increase in the media thickness. This suggests that an important means by which the morphological changes in hypertension are established is through a reorganization of the wall material around the lumen, a process known as "remodelling"; growth of smooth muscle may only have a minor role. In general, antihypertensive therapy increases the lumen diameter and decreases the media thickness to lumen diameter ratio; recent studies suggest that there may be drug specific effects on these variables.

Animals↗