The longevity gene mIndy (I'm Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms.

Reduced expression of the plasma membrane citrate transporter INDY (acronym I'm Not Dead, Yet) extends life span in lower organisms. Deletion of the mammalian Indy (mIndy) gene in rodents improves metabolism via mechanisms akin to caloric restriction, known to lower blood pressure (BP) by sympathoadrenal inhibition. We hypothesized that mIndy deletion attenuates sympathoadrenal support of BP.

C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits cardiac sympathetic neurotransmission and autonomic function.

Aims: B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPR-A) receptor signalling inhibits cardiac sympathetic neurotransmission, although C-type natriuretic peptide (CNP) is the predominant neuropeptide of the nervous system with expression in the heart and vasculature. We hypothesized that CNP acts similarly to BNP, and that transgenic rats (TGRs) with neuron-specific overexpression of a dominant negative NPR-B receptor would develop heightened sympathetic drive.

Methods And Results: Mean arterial pressure and heart rate (HR) were significantly (P < 0.

Preserved functional autonomic phenotype in adult mice overexpressing moderate levels of human alpha-synuclein in oligodendrocytes.

Mice overexpressing human alpha-synuclein in oligodendrocytes (MBP1-α-syn) recapitulate some key functional and neuropathological features of multiple system atrophy (MSA). Whether or not these mice develop severe autonomic failure, which is a key feature of human MSA, remains unknown. We explored cardiovascular autonomic regulation using long-term blood pressure (BP) radiotelemetry and pharmacological testing.

AVE 0991, a non-peptide Mas-receptor agonist, facilitates penile erection.

The renin-angiotensin system plays a crucial role in erectile function. It has been shown that elevated levels of angiotensin II contribute to the development of erectile dysfunction both in humans and in aminals. On the contrary, the heptapeptide angiotensin-(1-7) appears to mediate penile erection by activation of the Mas receptor.

Spinophilin regulates central angiotensin II-mediated effect on blood pressure.

Central angiotensin II (AngII) plays an important role in the regulation of the sympathetic nervous system. The underlining molecular mechanisms are largely unknown. Spinophilin (SPL) is a regulator of G protein-coupled receptor signaling.

Estrogen receptor-beta signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice.

We found earlier that deoxycorticosterone acetate-salt treatment causes blood pressure-independent left ventricular hypertrophy, but only in male mice. To test the hypothesis that the estrogen receptor-β (ERβ) protects the females from left ventricular hypertrophy, we treated male and female ERβ-deficient (ERβ(-/-)) mice and their male and female littermates (wild-type [WT]) with deoxycorticosterone acetate-salt and made them telemetrically normotensive with hydralazine. WT males had increased (+16%) heart weight/tibia length ratios compared with WT females (+7%) at 6 weeks.

Autonomic dysregulation in ob/ob mice is improved by inhibition of angiotensin-converting enzyme.

The leptin-deficient ob/ob mice are insulin resistant and obese. However, the control of blood pressure in this model is not well defined. The goal of this study was to evaluate the role of leptin and of the renin-angiotensin system in the cardiovascular abnormalities observed in obesity using a model lacking leptin.

Diabetic hypertensive leptin receptor-deficient db/db mice develop cardioregulatory autonomic dysfunction.

Leptin receptor-deficient db/db mice develop human type 2 diabetes mellitus, hypertension, and obesity with disrupted circadian blood pressure (BP) rhythm. Whether leptin is the sole mechanism mediating autonomic imbalance and hypertension is unclear. To explore this notion further, we measured BP by radiotelemetry combined with fast Fourier transformation and assessed autonomic function pharmacologically before and after renin-angiotensin system blockade with enalapril.

Fine tuning of blood pressure by the regulator of G protein signaling (RGS) 2.

G protein-coupled receptors (GPCRs) are expressed ubiquitously and involved in a variety of physiologic and pathologic processes. One of the key steps in the GPCR signaling cascade is the phosphorylation of the Galpha-subunit that triggers its dissociation from the Gbetagamma-subunit and from the receptor, allowing both G protein subunits to activate different downstream second messengers. Thereafter, Galpha hydrolyzes the attached guanosine triphosphate (GTP) to guanosine diphosphate (GDP) by its inherent enzymatic activity and terminates signaling.

Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice.

Objective: Epoxyeicosatrienoic acids (EETs) serve as endothelial-derived hyperpolarizing factors (EDHF), but may also affect vascular function by other mechanisms. We identified a novel interaction between EETs and endothelial NO release using soluble epoxide hydrolase (sEH) -/- and +/+ mice.

Methods And Results: EDHF responses to acetylcholine in pressurized isolated mesenteric arteries were neither affected by the sEH inhibitor, N-adamantyl-N'-dodecylurea (ADU), nor by sEH gene deletion.

Role of the multidomain protein spinophilin in blood pressure and cardiac function regulation.

Spinophilin controls intensity/duration of G protein-coupled receptor signaling and thereby influences synaptic activity. We hypothesize that spinophilin affects blood pressure through central mechanisms. We measured blood pressure and heart rate in SPL-deficient (SPL(-/-)), heterozygous SPL-deficient (SPL(+/-)), and wild-type (SPL(+/+)) mice by telemetry combined with fast Fourier transformation.

Deoxycorticosterone acetate-salt mice exhibit blood pressure-independent sexual dimorphism.

We tested the hypothesis that female and male mice differ in terms of cardiac hypertrophy after deoxycorticosterone acetate (DOCA)+salt hypertension (uninephrectomy and 1% saline in drinking water) and focused on calcineurin signaling. We excluded confounding effects of blood pressure elevation or sex-related blood pressure differences by treating DOCA-salt mice with hydralazine (250 mg/L in drinking water). We found that directly measured mean arterial blood pressure was lowered to control values with hydralazine and corroborated this finding in separate mouse groups with radiotelemetry.

Cardiovascular autonomic regulation in Non-Obese Diabetic (NOD) mice.

Non-Obese Diabetic (NOD) mice show profound pathomorphological changes in sympathetic ganglia during the development of type 1 diabetes mellitus. We tested the hypothesis that NOD mice represent an experimental model to investigate cardiovascular changes seen in humans with diabetic autonomic neuropathy. Blood glucose (BG) levels were measured once a week.

Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice.

Angiotensin II (Ang II) activates signalling pathways predominantly through the G-protein-coupled Ang II type 1 receptor (AT(1)R). The regulator of G protein signalling 2 (RGS2) is a negative G protein regulator. We hypothesized that RGS2 deletion changes blood pressure regulation by increasing the response to Ang II.

Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function.

The vasodilator/antiproliferative peptide angiotensin-(1-7) [ANG-(1-7)] is released into the corpus cavernosum sinuses, but its role in erectile function has yet to be defined. In this study, we sought to determine whether ANG-(1-7) and its receptor Mas play a role in erectile function. The ANG-(1-7) receptor Mas was immunolocalized in rat corpus cavernosum by confocal microscopy.