In obesity-related hypertension, activation of the renin-angiotensin system (RAS) has been reported despite marked fluid volume expansion. Adipose tissue expresses components of the RAS and is markedly expanded in obesity. This study evaluated changes in components of the adipose and systemic RAS in diet-induced obese hypertensive rats. RAS was quantified in adipose tissue and compared with primary sources for the circulating RAS. Male Sprague-Dawley rats were fed either a low-fat (LF; 11% kcal as fat) or moderately high-fat (32% kcal as fat) diet for 11 wk. After 8 wk, rats fed the moderately high-fat diet segregated into obesity-prone (OP) and obesity-resistant (OR) groups based on their body weight gain (body weight: OR, 566 +/- 10; OP, 702 +/- 20 g; P < 0.05). Mean arterial blood pressure was increased in OP rats (LF: 97 +/- 2; OR: 97 +/- 2; OP: 105 +/- 1 mmHg; P < 0.05). Quantification of mRNA expression by real-time PCR demonstrated a selective increase (2-fold) in angiotensinogen gene expression in retroperitoneal adipose tissue from OP vs. OR and LF rats. Similarly, plasma angiotensinogen concentration was increased in OP rats (LF: 390 +/- 48; OR: 355 +/- 24; OP: 530 +/- 22 ng/ml; P < 0.05). In contrast, other components of the RAS were not altered in OP rats. Marked increases in the plasma concentrations of angiotensin peptides were observed in OP rats (angiotensin II: LF: 95 +/- 31; OR: 59 +/- 20; OP: 295 +/- 118 pg/ml; P < 0.05). These results demonstrate increased activity of the adipose and systemic RAS in obesity-related hypertension.

Severe spinal cord injuries above mid-thoracic levels can lead to a potentially life-threatening hypertensive condition termed autonomic dysreflexia, which is often triggered by painful distension of pelvic viscera (bladder or bowel) and consequent sensory fiber activation, including nociceptive C-fibers. Interruption of tonically active medullo-spinal pathways after injury causes disinhibition of thoracolumbar sympathetic preganglionic neurons, and intraspinal sprouting of nerve growth factor (NGF)-responsive primary afferent fibers is thought to contribute to their hyperactivity. We investigated spinal levels that are critical for eliciting autonomic dysreflexia using a model of noxious colorectal distension (CRD) after complete spinal transection at the fourth thoracic segment in rats. Post-traumatic sprouting of calcitonin gene-related peptide (CGRP)-immunoreactive primary afferent fibers was selectively altered at specific spinal levels caudal to the injury with bilateral microinjections of adenovirus encoding the growth-promoting NGF or growth-inhibitory semaphorin 3A (Sema3a) compared with control green fluorescent protein (GFP). Two weeks later, cardio-physiological responses to CRD were assessed among treatment groups before histological analysis of afferent fiber density at the injection sites. Dysreflexic hypertension was significantly higher with NGF overexpression in lumbosacral segments compared with GFP, whereas similar overexpression of Sema3a significantly reduced noxious CRD-evoked hypertension. Quantitative analysis of CGRP immunostaining in the spinal dorsal horns showed a significant correlation between the extent of fiber sprouting into the spinal segments injected and the severity of autonomic dysreflexia. These results demonstrate that site-directed genetic manipulation of axon guidance molecules after complete spinal cord injury can alter endogenous circuitry to modulate plasticity-induced autonomic pathophysiology.

Human Type 2 diabetes is associated with increased incidence of hypertension and disrupted blood pressure (BP) circadian rhythm. Db/db mice have been used extensively as a model of Type 2 diabetes, but their BP is not well characterized. In this study, we used radiotelemetry to define BP and the circadian rhythm in db/db mice. We found that the systolic, diastolic, and mean arterial pressures were each significantly increased by 11, 8, and 9 mmHg in db/db mice compared with controls. In contrast, no difference was observed in pulse pressure or heart rate. Interestingly, both the length of time db/db mice were active (locomotor) and the intensity of locomotor activity were significantly decreased in db/db mice. In contrast to controls, the 12-h light period average BP in db/db mice did not dip significantly from the 12-h dark period. A partial Fourier analysis of the continuous 72-h BP data revealed that the power and the amplitude of the 24-h period length rhythm were significantly decreased in db/db mice compared with the controls. The acrophase was centered at 0141 in control mice, but became scattered from 1805 to 0236 in db/db mice. In addition to BP, the circadian rhythms of heart rate and locomotor activity were also disrupted in db/db mice. The mean arterial pressure during the light period correlates with plasma glucose, insulin, and body weight. Moreover, the oscillations of the clock genes DBP and Bmal1 but not Per1 were significantly dampened in db/db mouse aorta compared with controls. In summary, our data show that db/db mice are hypertensive with a disrupted BP, heart rate, and locomotor circadian rhythm. Such changes are associated with dampened oscillations of clock genes DBP and Bmal1 in vasculature.

Interactions of sympathetic nerve activity (SNA) with blood pressure (BP) and heart rate (HR) were assessed in conscious rats while they rested quietly in a cloth sock (n = 7), roamed freely in their home cage (n = 6), and then after anesthesia with pentobarbital (30 mg/kg; n = 7). The power and coherence spectra below 3 Hz were calculated from data collected for 9.56 min. In the conscious rat, SNA spectral power peaked at 0.4 Hz, whereas the majority of spectral power for both BP and HR occurred at frequencies lower than 0.4 Hz. However, there was an inconspicuous peak in the BP power spectra at 0.4 Hz that was not seen in the HR spectra. Coherence between SNA and BP peaked at a frequency of approximately 0.4 Hz, the same frequency at which the SNA spectral peaks occurred. In contrast, at frequencies below 0.4 Hz where maximum BP power occurred, the coherence was considerably lower. Anesthesia with pentobarbital lowered spectral power for BP, SNA, and HR but essentially did not change the coherence between SNA and BP. Interactions between respiration and each of the other variables were weak in the conscious rat. However, prominent respiratory interactions at approximately 1.2 Hz were evident after anesthesia. These data indicate a close coupling between SNA and BP at 0.4 Hz, raising the possibility that the BP spectral power at 0.4 Hz reliably reflects sympathetic activity.

The purpose of this study was to quantify the relative roles of the canine cardiac parasympathetic and sympathetic nerves in controlling the distribution of power within the heart rate (HR) power spectrum using a highly selective surgical technique to parasympathectomize the SA node. DAta were recorded in awake dogs (n = 6) before and after the selective denervation; the animals were isolated from human contact and their behavior carefully monitored during the measurements. The average amplitude in the high-frequency (approximately 0.32 Hz) peak in the HR power spectrum decreased from a predenervation control of 2.68 +/- 1.54 (mean +/- SD, arbitrary units) to 0.07 +/- 0.06 (P less than 0.05). Corresponding resting HR increased from 80 +/- 9 to 106 +/- 16 beats/min (P less than 0.05). The low-frequency peak (approximately 0.02 Hz) also decreased from a control of 2.45 +/- 1.18 to a postparasympathectomy value of 1.25 +/- 0.92 (P less than 0.05). beta-Adrenergic blockade (propranolol, 1 mg/kg) further decreased the latter peak to 0.59 +/- 0.52 (P less than 0.05). These data directly demonstrate that the high-frequency peak of the HR power spectrum 1) results from parasympathetic control of SA nodal automaticity, while 2) the low-frequency peak reflects activity in both divisions of the autonomic nervous system.