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C Aalkjaer

Publications and source records attributed to C Aalkjaer.

At least 19 recordsLinked to original sources
PubMed2005

Functional abnormalities in isolated arteries from Goto-Kakizaki and streptozotocin-treated diabetic rat models.

Several different rat models have been developed for both type 1 and type 2 diabetes with the aim of displaying specific traits of diabetes. For example, a review on nephropathy associated with type 2 diabetes included 16 different rodent models ; new models are still being developed. The large number of different models developed for different traits makes it difficult to choose the right model for a given study. It is often a problem that the models are not sufficiently characterized, which makes it easy to misinterpret data or even come to the wrong conclusions. In this brief review, we will concentrate on the functional responses obtained in vitro from mesenteric arteries and aortic segments from rat models of diabetes. Since it is beyond the scope of this review to overview all different rodent models of diabetes, we will focus on two commonly used models of diabetes, namely the streptozotocin (STZ)-induced type 1 diabetic rat model and the inbred type 2 diabetic Goto-Kakizaki (GK)-rat model.

Animals↗
PubMed2004

Sodium coupled bicarbonate transporters in the kidney, an update.

Recently five genes have been cloned, which code for sodium dependent bicarbonate transport proteins. These genes belong to the SLC4A gene family. This short review summarizes our knowledge of these gene products with respect to their renal distribution and function. The best characterized members are the SLC4A4 and SLC4A7. SLC4A4 codes for an electrogenic Na(+), HCO(3) (-)-cotransporter (NBCe1), which is present in the basolateral membranes of proximal tubules and is responsible for the bicarbonate efflux here, and thus about 80% of the renal bicarbonate reabsorption. SLC4A7 codes for an electroneutral NBC (called NBC3 and NBCn1), which is present basolaterally in the thick ascending limb and the distal part of the collecting ducts and in intercalated cells (either apically or basolaterally) in the connecting and collecting tubules. In the thick ascending limb NBCn1 may be important for NH(4) (+) reabsorption. SLCA5 codes for an electrogenic NBC (called NBC4 and NBCe2), which based on RT-PCR is located to the kidney but the exact localization awaits a good antibody. This is also the case for the SLC4A8 and SLC4A10 gene products, which are sodium dependent Cl(-), HCO(3) (-) exchangers. The recent development in this field substantially increases our understanding of the complex renal regulation of acid base status.

Acid-Base Equilibrium↗
PubMed2002

Immunolocalization of electroneutral Na(+)-HCO cotransporters in human and rat salivary glands.

Patterns of salivary HCO secretion vary widely among species and among individual glands. In particular, virtually nothing is known about the molecular identity of the HCO transporters involved in human salivary secretion. We have therefore examined the distribution of several known members of the Na(+)-HCO cotransporter (NBC) family in the parotid and submandibular glands. By use of a combination of RT-PCR and immunoblotting analyses, the electroneutral cotransporters NBC3 and NBCn1 mRNA and protein expression were detected in both human and rat tissues. Immunohistochemistry demonstrated that NBC3 was present at the apical membranes of acinar and duct cells in both human and rat parotid and submandibular glands. NBCn1 was strongly expressed at the basolateral membrane of striated duct cells but not in the acinar cells in the human salivary glands, whereas little or no NBCn1 labeling was observed in the rat salivary glands. The presence of NBCn1 at the basolateral membrane of human striated duct cells suggests that it may contribute to ductal HCO secretion. In contrast, the expression of NBC3 at the apical membranes of acinar and duct cells in both human and rat salivary glands indicates a possible role of this isoform in HCO salvage under resting conditions.

Animals↗
PubMed2001

Differential effects of angiotensin AT1 and AT2 receptors on the expression, translation and function of the Na+-H+ exchanger and Na+-HCO3- symporter in the rat heart after myocardial infarction.

OBJECTIVES: This study investigated the role of angiotensin receptor subtype 1 (AT1) and angiotensin receptor subtype 2 (AT2) in the regulation of Na+-H+ exchanger (NHE) and Na+-HCO3 symporter (NBC) in the infarcted myocardium. BACKGROUND: The cardiac renin-angiotensin system is activated after myocardial infarction (MI), and both angiotensin AT1 and AT2 receptors are upregulated in the myocardium. METHODS: Na+-H+ exchanger isoform-1 and NBC-1 gene expression were determined by reverse transcription polymerase chain reaction and Northern blot analysis; protein levels by Western blot analysis; and activity by measurement of H+ transport in left ventricular (LV) free wall, interventricular septum (IS) and right ventricle (RV) after induction of MI. Rats were treated with placebo, the angiotensin-converting enzyme inhibitor ramipril (1 mg/kg/day), the AT1 receptor antagonist valsartan (10 mg/kg/day) or the AT2 receptor antagonist PD 123319 (30 mg/kg/day). Treatment was started seven days before surgery. RESULTS: Na+-H+ exchanger isoform-1 and NBC-1 messenger RNA (mRNA) expression and protein levels were increased twofold in the LV free wall after MI, whereas no changes were observed in the IS and RV. Na+-dependent H+ flux was increased in the LV free wall. Ramipril inhibited mRNA and protein upregulation of both transporters. Valsartan inhibited the upregulation of NHE-1 mRNA and protein but had no effect on NBC-1 mRNA expression and translation. In contrast, PD 123319 abolished the upregulation of NBC-1 mRNA and protein but had no effect on NHE-1 upregulation. Ramipril and valsartan prevented post-MI increase in NHE-1 activity, whereas ramipril and PD 123319 decreased NBC-1 activity. CONCLUSIONS: Angiotensin II via its AT1 and AT2 receptors differentially controls transcriptional and translational regulation as well as the activity of NHE-1 and NBC-1 in the ischemic myocardium and contributes to the control of pH regulation in cardiac tissue.

Angiotensin I↗
PubMed2001

Hypothesis for the initiation of vasomotion.

Vasomotion is the regular variation in tone of arteries. In our study, we suggest a model for the initiation of vasomotion. We suggest that intermittent release of Ca(2+) from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is initially unsynchronized between the vascular smooth muscle cells, becomes synchronized to initiate vasomotion. The synchronization is achieved by an ion current over the cell membrane, which is activated by the oscillating Ca(2+) release. This current results in an oscillating membrane potential, which synchronizes the SR in the vessel wall and starts vasomotion. Therefore, the pacemaker of the vascular wall can be envisaged as a diffuse array of individual cytosolic oscillators that become entrained by a reciprocal interaction with the cell membrane. The model is supported by experimental data. Confocal [Ca(2+)](i) imaging and isometric force development in isolated rat resistance arteries showed that low norepinephrine concentrations induced SR-dependent unsynchronized waves of Ca(2+) in the vascular smooth muscle. In the presence of the endothelium, the waves converted to global synchronized oscillations of [Ca(2+)](i) after some time, and vasomotion appeared. Synchronization was also seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using the patch-clamp technique and microelectrodes, we showed that Ca(2+) release can activate an inward current in isolated smooth muscle cells from the arteries and cause depolarization. These electrophysiological effects of Ca(2+) release were cGMP dependent, which is consistent with the possibility that they are important for the cGMP-dependent synchronization. Further support for the model is the observation that a short-lasting current pulse can initiate vasomotion in an unsynchronized artery as expected from the model.

Animals↗
PubMed2001

Adrenergic responses in human small arteries isolated from the femoral neck.

Many pathological bone conditions are accompanied by changes in bone perfusion. However, no method has yet allowed investigation of vascular reactivity in human bone tissue. In the present study, arterial segments (diameter approximately 0.25 mm) were isolated from human bone biopsies and mounted as ring preparations in vitro. The viability of the arteries and the effects of adrenoceptor stimulations were investigated. Combined alpha- and beta-adrenoceptor stimulation (noradrenaline 10(-8)-10(-5) M) and specific alpha1-adrenoceptor stimulation (phenylephrine, 10(-8)-10(-4.5) M) induced concentration-dependent contractions in all arteries. Selective stimulation of alpha2-receptors (B-HT 933, 10(-8)-10(-3.5) M) only induced contraction in three of eight arteries. Stimulation of beta-receptors with isoprenaline (10(-6) M) resulted in vasorelaxation in 3 of 10 arteries. In all arteries, acetylcholine (10(-10)-10(-5) M) induced vasorelaxation, demonstrating preserved function of the endothelium. The results suggest that primarily alpha1-receptors are responsible for adrenoceptor induced vasoconstriction in human bone while functional alpha2- and beta-receptors may not be consistently expressed. The model is the first to allow investigations on vascular reactivity in human bone tissue and may become valuable for assessment of both normal and pathological bone physiology.

Acetylcholine↗
PubMed2001

Effects of oophorectomy on functional properties of resistance arteries isolated from the cancellous bone of the rabbit femur.

Information is sparse concerning the effect of oophorectomy (OOX) on bone vascularization and blood flow of possible significance for altered remodeling. Whether OOX affects functional characteristics of isolated bone resistance arteries was investigated. Ring preparations (diameter approximately 250 microm) of small femoral bone arteries from oophorectomized and sham-operated rabbits were mounted on a myograph six weeks postoperatively. Cumulative concentration response curves were obtained for various agonists at a normalized lumen diameter. Oophorectomy did not significantly influence lumen diameter, maximal response to high potassium, or maximal response to high potassium and 10(-5) M noradrenaline. However, OOX significantly increased the maximal response to noradrenaline (OOX 2.14 +/- 0.36 N/m, Sham 1.25 +/- 0.14 N/m) and endothelin-1 (OOX 1.76 +/- 0.32, Sham 0.95 +/- 0.15) in metaphyseal arteries. Moreover, the corresponding maximal active pressure for the agonists was significantly increased. OOX did not influence endothelial function assessed by the effects of acetylcholine or substance P. The functional responses of diaphyseal arteries were unaffected by OOX. The study demonstrates regional differences in the effects of OOX on small arteries of importance for control of vascular resistance in bone which suggests a relation between altered vascular function after ovarian hormonal withdrawal and the changes in bone turnover associated with osteoporosis.

Acetylcholine↗
PubMed2001

Endothelial dysfunction in resistance arteries is related to high blood pressure and circulating low density lipoproteins in previously treated hypertension.

BACKGROUND: Peripheral endothelial dysfunction has been demonstrated in hypertension. However, its relationship to blood pressure (BP) load, vascular structure, and metabolic disturbances in patients with long-standing, previously treated hypertension is unclear. METHODS: A total of 41 patients with stage I to III essential hypertension and electrocardiographic left ventricular hypertrophy were studied. After 2 to 3 weeks of placebo treatment we measured nitroprusside-induced relaxation (NIR), acetylcholine-induced relaxation (AIR), and media:lumen ratio in isolated, subcutaneous resistance arteries by myography, as well as 24-h ambulatory BP, and serum lipids. RESULTS: Maximal AIR correlated negatively with median 24-h diastolic BP (r=-0.42, P=.01), and sensitivity to AIR correlated negatively with serum low density lipoprotein (LDL) (r =-0.36, P < .05). In multiple regression analyses, sensitivity to AIR correlated negatively with serum LDL (beta=-0.33) independently of maximal NIR (beta=0.41) (adjusted R2 =0.26, P < .01). Maximal acetylcholine-induced relaxation correlated negatively with median 24-h diastolic BP (beta=-0.38) independently of maximal NIR (beta=0.45) (adjusted R2= 0.32, P < .001). Acetylcholine-induced relaxation was not significantly related to diabetes or to media:lumen ratio (r = -0.26, NS). CONCLUSIONS: High diastolic BP and high serum LDL were associated with impaired maximal AIR and reduced sensitivity to AIR, respectively, independently of smooth muscle cell responsiveness to nitroprusside. This indicated decreasing endothelial function in small resistance arteries with increasing BP and increasing LDL in hypertension. Endothelial function was not significantly related to vascular structure of the resistance arteries or to diabetes in these patients with long-standing hypertension.

Acetylcholine↗
PubMed2001

Molecular and functional evidence for electrogenic and electroneutral Na(+)-HCO(3)(-) cotransporters in murine duodenum.

Inward Na(+)-HCO(3)(-) cotransport has previously been demonstrated in acidified duodenal epithelial cells, but the identity and localization of the mRNAs and proteins involved have not been determined. The molecular expression and localization of Na(+)-HCO(3)(-) cotransporters (NBCs) were studied by RT-PCR, sequence analysis, and immunohistochemistry. By fluorescence spectroscopy, the intracellular pH (pH(i)) was recorded in suspensions of isolated murine duodenal epithelial cells loaded with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Proximal duodenal epithelial cells expressed mRNA encoding two electrogenic NBC1 isoforms and the electroneutral NBCn1. Both NBC1 and NBCn1 were localized to the basolateral membrane of proximal duodenal villus cells, whereas the crypt cells did not label with the anti-NBC antibodies. DIDS or removal of extracellular Cl(-) increased pH(i), whereas an acidification was observed on removal of Na(+) or both Na(+) and Cl(-). The effects of inhibitors and ionic dependence of acid/base transporters were consistent with both inward and outward Na(+)-HCO(3)(-) cotransport. Hence, we propose that NBCs are involved in both basolateral electroneutral HCO(3)(-) transport as well as basolateral electrogenic HCO(3)(-) transport in proximal duodenal villus cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel.

Two electroneutral, Na+-driven HCO3- transporters, the Na+-driven Cl-/HCO3- exchanger and the electroneutral Na+/HCO3- cotransporter, have crucial roles in regulating intracellular pH in a variety of cells, including cardiac myocytes, vascular smooth-muscle, neurons and fibroblasts; however, it is difficult to distinguish their Cl- dependence in mammalian cells. Here we report the cloning of three variants of an electroneutral Na+/HCO3- cotransporter, NBCn1, from rat smooth muscle. They are 89-92% identical to a human skeletal muscle clone, 55-57% identical to the electrogenic NBCs and 33-43% identical to the anion exchangers. When expressed in Xenopus oocytes, NBCn1-B (which encodes 1,218 amino acids) is electroneutral, Na+-dependent and HCO3(-)-dependent, but not Cl(-)-dependent. Oocytes injected with low levels of NBCn1-B complementary RNA exhibit a Na+ conductance that 4,4-diisothiocyanatostilbene-2,2'-disulphonate stimulates slowly and irreversibly.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Immunolocalization of electroneutral Na-HCO(3)(-) cotransporter in rat kidney.

An electroneutral Na-HCO(3)(-) cotransporter (NBC(N)1) was recently cloned, and Northern blot analyses indicated its expression in rat kidney. In this study, we determined the cellular and subcellular localization of NBC(N)1 in the rat kidney at the light and electron microscopic level. A peptide-derived antibody was raised against the COOH-terminal amino acids of NBC(N)1. The affinity-purified antibody specifically recognized one band, approximately 180 kDa, in rat kidney membranes. Peptide-N-glycosidase F deglycosylation reduced the band to approximately 140 kDa. Immunoblotting of membrane fractions from different kidney regions demonstrated strong signals in the inner stripe of the outer medulla (ISOM), weaker signals in the outer stripe of the outer medulla and inner medulla, and no labeling in cortex. Immunocytochemistry demonstrated that NBC(N)1 immunolabeling was exclusively observed in the basolateral domains of thick ascending limb (TAL) cells in the outer medulla (strongest in ISOM) but not in the cortex. In addition, collecting duct intercalated cells in the ISOM and in the inner medulla also exhibited NBC(N)1 immunolabeling. Immunoelectron microscopy demonstrated that NBC(N)1 labeling was confined to the basolateral plasma membranes of TAL and collecting duct type A intercalated cells. Immunolabeling controls were negative. By using 2, 7-bis-carboxyethyl-5,6-caboxyfluorescein, intracellular pH transients were measured in kidney slices from ISOM and from mid-inner medulla. The results revealed DIDS-sensitive, Na- and HCO(3)(-)-dependent net acid extrusion only in the ISOM but not in mid-inner medulla, which is consistent with the immunolocalization of NBC(N)1. The localization of NBC(N)1 in medullary TAL cells and medullary collecting duct intercalated cells suggests that NBC(N)1 may be important for electroneutral basolateral HCO(3)(-) transport in these cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Mechanisms of Ca2+ sensitization of force production by noradrenaline in rat mesenteric small arteries.

1. Mechanisms of Ca2+ sensitization of force production by noradrenaline were investigated by measuring contractile responses, intracellular Ca2+ concentration ([Ca2+]i) and phosphorylation of the myosin light chain (MLC) in intact and alpha-toxin-permeabilized rat mesenteric small arteries. 2. The effects of noradrenaline were investigated at constant membrane potential by comparing fully depolarized intact arteries in the absence and presence of noradrenaline. Contractile responses to K-PSS (125 mM K+) and NA-K-PSS (K-PSS + 10 microM noradrenaline) were titrated to 30 and 75%, respectively, of control force, by adjusting extracellular Ca2+ ([Ca2+]o). At both force levels, [Ca2+]i was substantially lower with NA-K-PSS than with K-PSS. With K-PSS, the proportion of MLC phosphorylated (approximately 30%) was similar at 30 and 75% of control force; with NA-K-PSS, MLC phosphorylation was greater at the higher force level (40 vs. 34%). 3. In alpha-toxin-permeabilized arteries, the force response to 1 microM Ca2+ was increased by 10 microM noradrenaline, and MLC phosphorylation was increased from 35 to 45%. The protein kinase C (PKC) inhibitor calphostin C (100 nM) abolished the noradrenaline-induced increase in MLC phosphorylation and contractile response, without affecting the contraction in response to Ca2+. Treatment with ATP gamma S in the presence of the MLC kinase inhibitor ML-9 increased the sensitivity to Ca2+ and abolished the response to noradrenaline. 4. The present results show that that in rat mesenteric small arteries noradrenaline-induced Ca2+ sensitization is associated with an increased proportion of phosphorylated MLC. The results are consistent with a decreased MLC phosphatase activity mediated through PKC. Furthermore, while MLC phosphorylation is a requirement for force production, the results show that other factors are also involved in force regulation.

Animals↗
PubMed1998

The role of [Ca2+]i, membrane potential and pHi in the relaxation of rat mesenteric arteries to hyperosmolar acetate.

In vitro both acetate and hyperosmolarity cause vasodilation, which could be physiologically important during food ingestion and during peritoneal dialysis. The purpose of this study was to investigate the role of the intracellular calcium concentration ([Ca2+]i, measured with fura-2), membrane potential (measured with glass microelectrodes) and intracellular pH [pHi, measured with bis-carboxyethylcarboxyfluorescein (BCECF)] in the vasodilation. Hyperosmolar sodium acetate (30 mM) concentration dependently relaxed noradrenaline-precontracted arteries. This response was associated with hyperpolarization and a fall in [Ca2+]i. In arteries precontracted with 50 mM K+ the relaxation was associated with a decrease of [Ca2+]i but no change in membrane potential. Isoosmolar sodium acetate neither relaxed or affect [Ca2+]i of K+-precontracted arteries, but induced a small relaxation with no reduction in [Ca2+]i in noradrenaline-precontracted arteries. Hyperosmolar acetate caused a transient reduction of pHi that was unrelated to relaxation. It is concluded that the mechanisms responsible for the relaxation to hyperosmolar acetate involve a decrease of [Ca2+]i, which is only partly explained by hyperpolarization and probably a decrease in the sensitivity of the contractile proteins to [Ca2+]i. pHi seems not to play a role in these effects.

Animals↗
PubMed1998

Effect of antihypertensive treatment on cardiac and subcutaneous artery structure: a comparison between calcium channel blocker and thiazide-based regimens.

The effects of two antihypertensive regimens (isradipine and hydrochlorothiazide-amiloride) on the ratio between media thickness and lumen diameter of subcutaneous arteries and on left ventricular mass in essential hypertension were compared. Fifty patients, aged 46.3+/-8 (mean+/-SD) years, with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with either isradipine or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added in both groups as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. A subcutaneous gluteal biopsy was taken surgically before medication and again after 9 months of successful antihypertensive treatment. Two small resistance arteries were isolated from each biopsy and mounted in a Mulvany-Halpem isometric small vessel myograph. The media thickness-to-lumen diameter ratio (percentage) of the vessels was measured under standardized conditions and meaned. Left ventricular mass (LVM) index was determined by echocardiography according to the Penn convention. Ten patients were treated with isradipine as monotherapy, whereas only one patient was well controlled on diuretics as monotherapy. Mean blood pressure was reduced equally with the two regimens, from 131+/-9 mm Hg to 101+/-10 mm Hg with the isradipine and from 128+/-9 mm Hg to 99+/-7 mm Hg with the thiazide/atenolol regimen. LVM decreased significantly in both groups by 130+/-75 g with the isradipine-based regimen and by 70+/-53 g with the hydrochlorothiazide/atenolol-based regimen. The reduction of LVM was significantly greater on the isradipine-based regimen than on the thiazide-based regimen (P < .01). There was a significant reduction of media thickness-to-lumen diameter ratio during treatment with the isradipine-based regimen from 10.9% to 8.8% (P < .01). The reduction in the thiazide regimen was from 9.7% to 8.5%, which was not significant (P = .07). The study demonstrated significant reduction of hypertensive changes in peripheral resistance artery structure during antihypertensive treatment with an isradipine-based regimen. The thiazide/betablocker-based regimen did not have a significant effect on the vessels. Significant reduction of LVM was achieved with both isradipine-based and thiazide/atenolol-based regimens. The reduction of LVM obtained with the isradipine-based regimen was significantly greater than that of the thiazide/atenolol-based regimen.

Adult↗
PubMed1998

Differential regulation of ventricular adrenomedullin and atrial natriuretic peptide gene expression in pressure and volume overload in the rat.

1. Adrenomedullin is a recently discovered vasodilating and natriuretic peptide whose physiological and pathophysiological roles remain to be established. Like atrial natiuretic peptide adrenomedullin is expressed in the left ventricle. Ventricular expression of atrial natriuretic peptide is known to be markedly increased by volume or pressure overload. In this study we investigated whether ventricular expression of adrenomedullin is similarly stimulated under such conditions. 2. Ventricular adrenomedullin and atrial natriuretic peptide mRNA levels as well as those of a loading control mRNA (glyceraldehyde-3-phosphate dehydrogenase) were quantified by Northern blot analysis in (a) rats with severe post-infarction heart failure induced by left coronary ligation at 30 days post-surgery and (b) in rats with pressure-related cardiac hypertrophy induced by aortic banding at several time points (0.5, 1 and 4 h, and 1, 4, 7 and 28 days) after surgery. Levels were compared with those in matched sham-operated controls. 3. The mRNA level of atrial natriuretic peptide was markedly increased (8-10-fold) in the left ventricle of animals with post-infarction heart failure. In contrast, there was only a modest (40%) increase in the level of adrenomedullin mRNA. In rats with pressure-induced cardiac hypertrophy the ventricular level of atrial natriuretic peptide mRNA was again markedly increased (maximum 10-fold). The increase was first noticeable at 24 h post-banding and persisted until 28 days. In contrast, there was no change in adrenomedullin mRNA level compared with sham-operated rats at any time point. 4. Despite having similar systemic effects, the expression of adrenomedullin and atrial natriuretic peptide in the left ventricle is differently regulated. The findings imply distinct roles for the two peptides. The results do not support an important role for ventricular adrenomedullin expression in the remodelling process that occurs during the development of cardiac hypertrophy but suggest that ventricular adrenomedullin participates in the local and/or systemic response to heart failure.

Adrenomedullin↗
PubMed1998

On the cellular mechanism for the effect of acidosis on vascular tone.

The role of smooth muscle [Ca2+]i and membrane potential for the relaxation to hypercapnic (increased CO2) and normocapnic (unchanged CO2) acidosis is not complete understood. It is often stated that membrane hyperpolarization plays an important role but this has not been vigorously tested. In this study we investigated isolated rat cerebral small arteries under isobaric conditions. Lumen diameter was measured simultaneously with either [Ca2+]i or membrane potential, and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution or by adding HCI to a nominally bicarbonate-free solution. Confocal microscopy verified loading of smooth muscle cells with fluorescent dyes. Acidosis always reduced myogenic tone at transmural pressures between 20 and 120 mmHg. Acidification at a transmural pressure of 40 mmHg caused an increase in diameter and a decrease in [Ca2+]i. This was also seen in the presence of L-NNA and after depolarization with 50 mM K+. The response to hypercapnic and normocapnic acidosis was similar. However, while hypercapnic acidosis caused hyperpolarization, normocapnic acidosis caused depolarization. Dilatation, decrease of [Ca2+]i and depolarization, was also seen with reduction of pH in bicarbonate-free solution. We conclude that the isobaric relaxation to both hypercapnic and normocapnic acidosis is most likely mediated by a reduction of [Ca2+]i. Membrane potential may on the other hand not play a major role for this reduction of [Ca2+]i and it is possible that molecular CO2 has an effect on the membrane potential.

Acidosis↗