In Dahl salt-sensitive (S) and salt-resistant (R) rats, and spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, at 5-6 wk of age, a cannula was placed in the cisterna magna, and cerebrospinal fluid (CSF) was withdrawn continuously at 75 microl/12 h. CSF was collected as day- and nighttime samples from rats on a regular salt intake (0.6% Na+; R-Na) and then on a high salt intake (8% Na+; H-Na). In separate groups of rats, the abdominal aorta was cannulated and blood pressure (BP) and heart rate (HR) measured at 10 AM and 10 PM, with rats first on R-Na and then on H-Na. On H-Na, CSF [Na+] started to increase in the daytime of day 2 in Dahl S rats and of day 3 in SHR. BP and HR did not rise until day 3 in Dahl S rats and day 4 in SHR. In Dahl R and WKY rats, high salt did not change CSF [Na+], BP, or HR. In a third set of Dahl S rats, sampling of both CSF and BP was performed in each individual rat. Again, significant increases in CSF [Na+] were observed 1-2 days earlier than the increases in BP and HR. In a fourth set of Dahl S rats, BP and HR were recorded continuously by means of radiotelemetry for 5 days on R-Na and 8 days on H-Na. On H-Na, BP (but not HR) increased first in the nighttime of day 2. In another set of Dahl S rats, intracerebroventricular infusion of antibody Fab fragments binding ouabain-like compounds (OLC) with high affinity prevented the increase in BP and HR by H-Na but further increased CSF [Na+]. Finally, in Wistar rats on H-Na, intracerebroventricular infusion of ouabain increased BP and HR but decreased CSF [Na+]. Thus, in both Dahl S and SHR on H-Na, increases in CSF [Na+] preceded the increases in BP and HR, consistent with a primary role of increased CSF [Na+] in the salt-induced hypertension. An increase in brain OLC in response to the initial increase in CSF [Na+] appears to attenuate further increases in CSF [Na+] but at the "expense" of sympathoexcitation and hypertension.

The purpose of the present study was to characterize in detail the 24 h blood pressure (BP) phenotype of mice lacking the gene for endothelial nitric oxide synthase (eNOS_/_) and the corresponding control strain (C57Bl/6J). Twenty-four hour BP recordings were made in conscious 12-to 16-week-old male mice 10 days following the implantation of a BP telemeter (n = 9 per group). The BP and heart rate of both strains were markedly affected by brief locomotor activity cycles, resulting in bimodal distributions of BP and heart rate within both light and dark periods. Data from active periods were associated with the higher of the two modes, whereas data from inactive periods were associated with the lower of the two modes. In eNOS_/_ mice, the 24 h average BP level was significantly elevated (+15 %, 104 ± 2 vs. 119 ± 1 mmHg), as was its daily range (+44 %), its coefficient of variation (+26 %), dark-light difference (+48 %), and the separation of the two modes of its distribution (+41 %). Pulse pressure was also significantly greater (+23 %) in eNOS_/_ mice. The 24 h heart rate level did not differ between control and eNOS_/_ mice. Considerable variation was noted among previously published values of BP in eNOS_/_ mice, but not in the corresponding control mice. Our results indicate that eNOS_/_ mice have mild hypertension that is accompanied by more pronounced increases in BP lability and/or reactivity. Our results also demonstrate a marked effect of locomotor activity on BP in mice, which may confound short-term measurements of BP.

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Since the first recording of sympathetic nerve activity (SNA) early last century, numerous methods for presentation of the resulting data have developed. In this paper, we discuss the common ways of describing SNA and their application to chronic recordings. Suggestions on assessing the quality of SNA are made, including the use of arterial pressure wave-triggered averages and nasopharyngeal stimuli. Calculation of the zero level of the SNA signal from recordings during ganglionic blockade, the average level between bursts and the minimum of arterial pressure wave-triggered averages are compared and shown to be equivalent. The use of normalization between zero and maximal SNA levels to allow comparison between groups is discussed. We recommend that measured microvolt levels of integrated SNA be presented (with the zero/noise level subtracted), along with burst amplitude and frequency information whenever possible. We propose that standardization of the quantifying/reporting of SNA will allow better comparison between disease models and between research groups and ultimately allow data to be more reflective of the human situation.

Recent studies have indicated that chronic administration of iV"-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, produces marked hypertension. Although the mechanism of this form of hypertension is not well understood, several studies have demonstrated that sympathetic nerve activity is at least acutely elevated after L-NAME administration. To evaluate the potential role of the renal sympathetic nerves in L-NAMEinduced hypertension, we compared the blood pressure response to L-NAME in four groups of Sprague-Dawley rats (n=8 each): (1) sham-operated vehicle-treated, (2) shamoperated L-NAME-treated, (3) denervated vehicle-treated, and (4) denervated L-NAME-treated. After renal denervation or sham surgery, L-NAME was added to the drinking N itric oxide (NO) is now known to be an important participant in a variety of physiological processes, including several that influence arterial pressure.1 Acute administration of substituted arginine analogues that inhibit NO synthesis, including /V°'-nitro-Larginine methyl ester (L-NAME), results in a prompt increase in arterial pressure.2 -3 The immediate increase in arterial pressure may be principally due to an increased vascular smooth muscle tone as a consequence of decreased endothelial synthesis of NO. Increases in sympathetic nerve activity have been described after acute NO synthesis inhibition, 46 suggesting that neurogenic mechanisms may also contribute to the acute increase in arterial pressure.Several laboratories have recently reported that continued administration of inhibitors of NO synthesis induces a sustained hypertension.79 Although a precise mechanism by which continued NO synthesis inhibition may induce chronic hypertension remains to be identified, renal control of fluid and electrolyte balance is thought to play a dominant role in the long-term control of arterial pressure in both normal and pathophysiological states.10 ' 11 Renal sympathetic nerve activity is known to be increased at least acutely after administration of NO synthesis inhibitor, 46 and activation of the renal sympathetic nerves is known to inhibit renal sodium excretion and promote renal renin secretion. 12 Thus, we hypothesized that chronic L-NAME-induced hypertension may be, in part, the result of a sustained activation of the renal sympathetic nerves and the resultant resetting of renal fluid and electrolyte balance water (70 rngVlOO mL) for 4 weeks, and arterial pressure was measured weekly by the tail-cuff method. L-NAME treatment caused a progressive increase in arterial pressure in shamoperated rats, rising to 154±6 mm Hg by week 4 of treatment compared with 115±2 mm Hg in the vehicle-treated shamoperated group (P<.005). In contrast, the development of hypertension was significantly delayed and attenuated in renaldenervated rats treated with L-NAME. The results of our study suggest that L-NAME-induced hypertension may be partly mediated by or is at least dependent on the integrity of the renal nerves. Key Words • blood pressure • end...

With the publication in 1972 of a large computer model of circulatory control, Guyton and colleagues challenged the then prevailing views on how blood pressure and cardiac output were controlled. At that time, it was widely accepted that the heart controlled cardiac output and that peripheral resistance controlled arterial blood pressure. By incorporating the empirically demonstrated concepts of blood flow autoregulation and the pressure–natriuresis relationship into their mathematical model, Guyton and colleagues were able to develop a number of revolutionary concepts. Guyton's circulatory model was particularly instrumental in exploring the linkage between blood pressure and sodium balance and in demonstrating an overriding importance of renal salt and water balance in setting the long‐term blood pressure level. In both the model and experimental data, any long‐lasting imbalance between salt intake and salt excretion leads to a progressive alteration of the degree of filling of the vascular system and thus to parallel changes in blood pressure. In turn, changes in blood pressure alter sodium excretion, opposing the initial salt imbalance. Although Guyton's model does not include the most recent cardiovascular discoveries, the concepts underlying the basic functioning of the cardiovascular system can serve as a well‐built basis for the development of new, large and integrative cardiovascular models.

We investigated why resting heart rate is elevated in dogs fed a high saturated fat diet for 12.7 +/- 1.8 wk. Obese dogs exhibited elevated body weight (59%), blood pressure (14%), and heart rate (25%). Differences in resting heart rate (control, 58 +/- 5 beats/min; obese, 83 +/- 7 beats/min) were abolished after hexamethonium, indicating an autonomic mechanism. Hexamethonium also reduced blood pressure in obese (20 +/- 4 mmHg) but not control (9 +/- 6 mmHg) animals. Propranolol did not affect heart rate in either group, excluding a beta-adrenergic mechanism. Subsequent administration of atropine increased heart rate more in control than in obese dogs (110 +/- 9 vs. 57 +/- 11 beats/min). The sensitivity of the cardiac limb of the baroreflex (Oxford method) was reduced by 46% in the obese group, confirming impairment of the parasympathetic control of heart rate. The standard deviation of blood pressure measurements was normal when expressed as a percentage of the mean arterial blood pressure (control, 11.2 +/- 0.4%; obese, 11.2 +/- 0.5%). Our results indicate that the development of obesity in dogs fed a high saturated fat diet is accompanied by an attenuated resting and reflex parasympathetic control of heart rate.

We investigated cardiac morphometry 6 wk after sinoaortic baroreceptor denervation (SAD) in Long-Evans rats. SAD (n = 19) was associated with an 11% increase in the weight of the left ventricle (LV) plus septum (P < 0.001) and a 39% increase in that of the right ventricular (RV) free wall (P < 0.001), relative to sham-operated rats (n = 18). RV wall thickness was significantly increased in SAD animals, but there was no difference in the LV wall thickness and volumes of the RV and LV between groups. Constrictor responses to methoxamine and dilation responses to acetylcholine were assessed in an in vitro perfused mesenteric circulation preparation, but neither response was affected by SAD. Baroreceptor denervation was associated with marked and significant increases in the variability (2.8-fold) and daily peak (39 mmHg) levels of telemetered mean arterial pressure (MAP) and small (5%) but significant increases in the daily mean MAP level. Our results are consistent with an effect of increased MAP variability on ventricular weight but cannot rule out possible contributions from other mechanisms.