PubMed Health⌕ Search

Biomedical subjects

Douglas S Martin

Publications and source records attributed to Douglas S Martin.

11 recordsLinked to original sources
PubMed2006

Androgens potentiate renal vascular responses to angiotensin II via amplification of the Rho kinase signaling pathway.

OBJECTIVES: This study assessed whether the Rho kinase signaling pathway contributes to androgenic amplification of angiotensin II (Ang II) induced pressor and renal constrictor responses. METHODS: Mean arterial pressure (MAP) responses to angiotensin II receptor 1 (AT1) inhibition were measured in conscious male New Zealand genetically hypertensive rats (NZGH) subjected to sham operation, castration or castration+testosterone replacement. MAP and renal vascular resistance (RVR) responses to Ang II were recorded with and without a Rho kinase inhibitor, fasudil, in anesthetized NZGH. Western blot was used to analyze target protein expression in the kidney. RESULTS: MAP responses to AT1 receptor inhibition and exogenous Ang II were attenuated in castrated NZGH. The increase in RVR (mm Hg/ml/min/g kidney) at the maximum dose of Ang II was significantly lower in castrated NZGH than in sham operated NZGH. Testosterone replacement restored RVR responses to Ang II in castrated rats. Fasudil treatment reduced both MAP and RVR responses to Ang II in each group. In addition, the differential MAP and RVR responses to Ang II amongst the three groups were significantly attenuated by Rho kinase inhibition. Western blot showed that Rho kinase protein expression was reduced by castration, while testosterone replacement restored the Rho kinase protein levels in castrated rats. The phosphorylation of myosin phosphatase target subunit 1 (MYPT1), a downstream target of Rho kinase, was also increased by androgens. CONCLUSIONS: Collectively, these results indicate that androgens potentiate Ang II-induced renal vascular responses, an effect mediated at least partly via up-regulation of the Rho kinase signaling pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2006

Androgens augment renal vascular responses to ANG II in New Zealand genetically hypertensive rats.

Males develop higher blood pressure than do females. This study tested the hypothesis that androgens enhance responsiveness to ANG II during the development of hypertension in New Zealand genetically hypertensive (NZGH) rats. Male NZGH rats were obtained at 5 wk of age and subjected to sham operation (Sham) or castration (Cas) then studied at three age groups: 6-7, 11-12, and 16-17 wk. Mean arterial blood pressure (MAP), heart rate (HR), and renal blood flow (RBF) measurements were recorded under Inactin anesthesia. These variables were measured after enalapril (1 mg/kg) treatment and during intravenous ANG II infusion (20, 40, and 80 ng/kg/min). Plasma testosterone was measured by ELISA. Angiotensin type 1 (AT1) receptor expression was assessed by Western blot analysis and RT-PCR. ANG II-induced MAP responses were significantly attenuated in Cas NZGH rats. At the highest ANG II dose, MAP increased by 40+/-4% in Sham vs. 22+/-1% in Cas NZGH rats of 16-17 wk of age. Similarly, renal vascular resistance (RVR) responses to ANG II were reduced by castration (209+/-20% in Sham vs. 168+/-10% in Cas NZGH rats at 16-17 wk of age). Castration also reduced MAP recorded in conscious NZGH rats of this age group. Testosterone replacement restored baseline MAP and the pressor and RVR responses to ANG II. Castration reduced testosterone concentrations markedly. Testosterone treatment restored these concentrations. Neither castration nor castration+testosterone treatment affected AT1 receptor mRNA or protein expression. Collectively, these data suggest that androgens modulate renal and systemic vascular responsiveness to ANG II, which may contribute to androgen-induced facilitation of NZGH rat hypertension.

Age Factors↗
PubMed2006

Rho kinase contributes to androgen amplification of renal vasoconstrictor responses in the spontaneously hypertensive rat.

Androgens modulate vascular tone and hypertension development. Rho kinase contributes to norepinephrine- (NE) and vasopressin- (AVP) induced vasoconstriction. This study tested the hypothesis that Rho kinase contributes to androgen amplification of renal vasoconstrictor responses to NE or AVP in isolated perfused kidney of spontaneously hypertensive rats (SHRs).SHRs (5 weeks) underwent sham operation, castration, or castration with testosterone replacement. At 16-17 weeks, mean arterial pressure and heart rate were measured in conscious SHRs. Renal vascular reactivity to NE (10 to 10 mol) and to AVP (10 to 10 mol) was assessed in an isolated perfused kidney preparation before and after Rho kinase inhibitor treatment (fasudil; 15 microM). Castration reduced mean arterial pressure, whereas testosterone treatment of castrated SHRs increased mean arterial pressure significantly. The dose-response curves to NE and AVP obtained in isolated perfused kidneys from castrated SHRs were displaced to the right of those obtained in sham-operated and castrated + testosterone-treated SHRs. Fasudil treatment produced a rightward shift in the dose-response curves for each agonist in all of the groups and greatly attenuated the differences in renal vascular reactivity to NE and AVP among the 3 groups of SHRs.Collectively, these findings indicate that androgen modulation of hypertension development in the SHR involves a fasudil-sensitive pathway and suggest that further study is warranted in this area.

Androgens↗
PubMed2004

Fructose feeding and intermittent hypoxia affect ventilatory responsiveness to hypoxia and hypercapnia in rats.

We hypothesized that, in male rats, 10% fructose in drinking water would depress ventilatory responsiveness to acute hypoxia (10% O2 in N2) and hypercapnia (5% CO2 in O2) that would be depressed further by exposure to intermittent hypoxia. Minute ventilation (Ve) in air and in response to acute hypoxia and hypercapnia was evaluated in 10 rats before fructose feeding (FF), during 6 wk of FF, and after FF was removed for 2 wk. During FF, five rats were exposed to intermittent air and five to intermittent hypoxia for 13 days. Six rats given tap water acted as control and were exposed to intermittent air and subsequently intermittent hypoxia. In FF rats, plasma insulin levels increased threefold in the rats exposed to intermittent hypoxia and during washout returned to levels observed in rats exposed to intermittent air. During FF, ventilatory responsiveness to acute hypoxia was depressed because of decreased tidal volume (Vt) responsiveness. During washout, Ve decreased as a result of decreased Vt and frequency of breathing, and the ventilatory responsiveness to hypoxia in intermittent hypoxia rats did not recover. In all rats, the ventilatory responses to hypercapnia were decreased during FF and recovered after washout because of an increased Vt responsiveness. In the control group, hypoxic responsiveness was not depressed after intermittent hypoxia and was augmented after washout. Thus FF attenuated the ventilatory responsiveness of conscious rats to hypoxia and hypercapnia. Intermittent hypoxia interacted with FF to increase insulin levels and depress ventilatory responses to acute hypoxia that remained depressed during washout.

Adaptation, Physiological↗
PubMed2003

Vascular ECE-1 mRNA expression decreases in response to estrogens.

DNA microarrays were used to identify new targets of estrogen in the vasculature. Ovariectomized rats were treated with estradiol, genistein or daidzein, for four days. [33P]dCTP-labelled probes synthesized from mesenteric artery RNA were hybridized with DNA microarrays. Analysis of the microarray data identified endothelin converting enzyme-1 (ECE-1) as a gene whose expression was inhibited by treatment with estrogen, genistein, or daidzein. Semi-quantitative RT-PCR was used to confirm the data from the DNA microarrays. Reversal of the estrogen and phytoestrogen effect on ECE-1 expression by ICI 182,780 suggested that the inhibition was an estrogen receptor response. An inhibition of ECE-1 mRNA expression by estrogen or the phytoestrogens has not been previously reported. These data highlight the power of DNA microarray technology to identify new gene expression targets of estrogen in the vasculature. Moreover, the data suggest that genistein and daidzein inhibit ECE-1 expression by an estrogen receptor-mediated mechanism.

Animals↗
PubMed2003

Estrogen decreases biglycan mRNA expression in resistance blood vessels.

This study was designed to identify new gene targets of estrogen in the mesenteric arteries and to determine whether the soy phytoestrogens could mimic estrogen effects. Ovariectomized rats were treated with estradiol, genistein, or daidzein for 4 days. The mesenteric arteries were harvested, total RNA was extracted, mRNA was reverse transcribed in the presence of [33P]dCTP, and the labeled probes were hybridized with DNA microarrays. Analysis of the microarray data identified biglycan as a target of estrogenic regulation. Semiquantitative RT-PCR was used to confirm and quantitate the decrease in biglycan gene expression in response to estrogen (-37%), genistein (-15%), and daidzein (-10%). Treatment with the pure estrogen receptor antagonist ICI-182,780 reversed the inhibition of biglycan gene expression. The decrease in biglycan gene expression in response to estrogens was paralleled with a decrease in biglycan protein expression. Biglycan protein was localized to the media of the mesenteric arteries by immunohistochemistry. Collectively, these data suggest that biglycan is a vascular protein regulated at the genomic level by estrogens.

Animals↗
PubMed2002

Apparent subdiffusion inherent to single particle tracking.

Subdiffusion and its causes in both in vivo and in vitro lipid membranes have become the focus of recent research. We report apparent subdiffusion, observed via single particle tracking (SPT), in a homogeneous system that only allows normal diffusion (a DMPC monolayer in the fluid state). The apparent subdiffusion arises from slight errors in finding the actual particle position due to noise inherent in all experimental SPT systems. A model is presented that corrects this artifact, and predicts the time scales after which the effect becomes negligible. The techniques and results presented in this paper should be of use in all SPT experiments studying normal and anomalous diffusion.

Biophysical Phenomena↗
PubMed2002

Pressor responsiveness to angiotensin in soy-fed spontaneously hypertensive rats.

Dietary soy may attenuate the development of arterial hypertension. In addition, some soy-containing foods exhibit angiotensin-converting enzyme (ACE) inhibitory properties. Accordingly, we tested the hypothesis that ACE inhibition contributes to the antihypertensive effect of dietary soy. Mean arterial blood pressure (MAP) was recorded from conscious spontaneously hypertensive rats (SHR) at least 24 h after the implantation of catheters. Cumulative dose-response curves to intravenous angiotensin I (AI) (5-100 ng x kg(-1) x min(-1)) and angiotensin II (AII) (1-20 ng x kg(-1) x min(-1)) were constructed for male, sham-operated female, and ovariectomized female (OVX) SHR that were maintained on either casein or soy diets. The soy diet was associated with a significant reduction in baseline MAP in the OVX SHR (approximately 20 mmHg, 1 mmHg = 133.322 Pa). AI and AII infusions caused graded increases in MAP in all groups. However, there was no significant attenuation of the pressor responses to AI in the soy-fed SHR. Conversely, we observed a significant rightward displacement of the AII dose-response curves in the soy-fed sham-operated and OVX SHR. We conclude that ACE inhibition does not account for the antihypertensive effect of dietary soy in mature SHR.

Angiotensin I↗
PubMed2002

Teaching human cardiovascular and respiratory physiology with the station method.

We have developed a station method to offer combined cardiovascular and respiratory physiology exercises all in one laboratory period during our medical physiology course. This laboratory was designed for first-year medical students in order to minimize equipment costs, maximize efficient use of both student and faculty time, and facilitate integration of basic cardiovascular concepts with those in respiratory physiology. We designed six stations for the students to evaluate: cardiovascular and respiratory responses to dynamic exercise, cold pressor reflex, postural influences and respiratory modulation of cardiovascular functions, forced expiratory maneuvers with inverted bell spirometers, forced expiratory maneuvers and maximal inspiratory maneuvers with electronic spirometers with and without obstruction, and respiratory muscle strength. Students worked in groups of two to four and were assessed by individual laboratory reports. Although we neglected to formally assess the impact on students of changes in laboratory design, students appeared to respond enthusiastically to the laboratory and prepared knowledgeable laboratory reports.

Cardiovascular Physiological Phenomena↗
PubMedDate not supplied

A method for the extraction of high-quality RNA and protein from single small samples of arteries and veins preserved in RNAlater.

INTRODUCTION: The mesenteric vasculature plays an important role in cardiovascular homeostasis, both in terms of arterial resistance and venous capacitance. However, the limited quantity of tissue available and the activity of RNases and proteases during dissection of the vessels make it difficult to study gene and protein expression in this tissue. METHODS: The mesenteric arcade was harvested from rats. The mesenteric arteries and veins were separated from each other and from contaminating adipose, nerve, and connective tissue by blunt dissection while submerged in RNAlater (Ambion). Total ribonucleic acid (RNA) and protein were extracted from the same mesenteric artery and vein samples. RESULTS: Good quality RNA and protein were obtained by this method. The method preserved the content of proteins including biglycan, adrenergic receptors, estrogen receptors, and protein kinase Cdelta, and also preserved the differential expression of estrogen receptors. DISCUSSION: A method for the isolation of high-quality RNA and protein from the arteries and veins of the same mesenteric sample is described. The content of proteins from a variety of cellular compartments and molecular weights was preserved by this method, as well as differential expression of proteins. This method will facilitate the study of gene and protein expression in the mesenteric vasculature in response to pharmacologic treatments and in disease states.

Animals↗