Joseph R. Haywood

Development of techniques for the continuous measurement of regional blood flow and vascular resistance in intact small animals has been impeded primarily by the bulkiness of flow probes. The availability of an ultrasonic pulsed Doppler flowmeter system enabled us to construct miniaturized probes using 1-mm-diameter piezoelectric crystals that emit a 20-mHz signal and receive the reflected sound waves from passing blood cells. The finished flow probe is approximately 2.5-4 mm long and 2 mm in cross-sectional diameter with lumen diameters appropriate for the rat, ranging from 0.7 to 1.2 mm. This report describes the materials and methods involved in constructing and implanting the probes in rats to monitor renal, mesenteric, and hindquarter blood flow velocity. The accuracy of the pulsed Doppler method in detecting changes in regional blood flow and vascular resistance was established by the demonstration of a highly significant correlation between velocity recorded from the Doppler unit and volume flow recorded simultaneously. These data indicate that the ultrasonic pulsed Doppler flowmeter provides the opportunity to measure changes in regional blood flow and vascular resistance in a conscious freely moving rat.

1. Females are protected against the development of hypertension. The purpose of the current review is to present the evidence for gender differences in the regulation of the sympatho-adrenal nervous system and to determine if these differences support the hypothesis that, in females, the regulation of the sympathetic nervous system (SNS) is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented. 2. The central control of sympatho-adrenal function is different in females and responses vary during the oestral and menstrual cycles. Pathways regulating the SNS appear to be less sensitive to excitatory stimuli and more sensitive to inhibitory stimuli in females compared with males. 3. Gender differences in arterial baroreflex sensitivity suggest that females may have a greater baroreflex sensitivity, such that alterations in blood pressure are more efficiently controlled than in males. Cardiopulmonary reflex inhibition of sympathetic nerve activity is greater in females, possibly resulting in a greater renal excretory function. 4. An attenuated sensitivity to adrenergic nerve stimulation, but not to noradrenaline (NA), suggests that gender differences in noradrenergic neurotransmission may protect females against sympathetic hyperactivity. Gender differences in the regulation of NA release via presynaptic alpha 2-adrenoceptors, the vasoconstrictor response to the cotransmitter neuropeptide Y and the clearance of catecholamines are consistent with this hypothesis. 5. Similarly, attenuated stress-induced increases in plasma catecholamines in women suggest that females are less sensitive and/or less responsive to adrenal medullary activation. This is supported by findings of gender differences in adrenal medullary catecholamine content, release and degradation. 6. We conclude that there is strong evidence that supports the hypothesis that, in females, the regulation of the SNS is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented.

The ovariectomized (OVX) Dahl salt-sensitive (DS) rat fed a low-salt diet is a model of postmenopausal hypertension. In addition to estrogen loss, aging can also contribute to postmenopausal hypertension. We hypothesized that: (1) female DS rats on a low-salt diet become hypertensive with age; (2) ovariectomy accelerates age-dependent hypertension in the DS rat caused by estrogen depletion; and (3) this hypertension correlates with increased type 1 angiotensin receptor (AT1R) number (Bmax). Blood pressure was monitored by telemetry from 3 to 12 months and AT1R Bmax was determined by Scatchard analysis in glomeruli and adrenal cortex. Three groups of DS rats were studied: intact, OVX, and 17beta-estradiol-replaced OVX (OVX+E). In intact rats, aging to 12 months resulted in hypertension (159+/-6 mm Hg) and an 82% decrease in estrogen. Blood pressure in OVX was significantly higher than OVX+E through 12 months of age (173+/-4 versus 150+/-8 mm Hg). At 4 months, OVX increased AT1R Bmax compared with intact and OVX+E in both glomeruli and adrenal cortex. Aging also increased AT1R Bmax in these tissues in intact rats. In summary, female DS rats fed a low-salt diet have hypertension develop with age, that is accelerated by OVX and attenuated by estrogen replacement. Concurrently, AT1Rs are upregulated by age and OVX, which is prevented by estrogen replacement. This study suggests that an increased activity of the renin angiotensin system contributes to the development of hypertension, and estrogen protects against this process.

This study compares the effect of arginine-vasopressin with phenylephrine on arterial pressure, heart rate, and renal sympathetic nerve activity in conscious rabbits with and without functional arterial baroreflexes and in rabbits with lesions of the area postrema. In intact rabbits, progressive infusions of arginine-vasopressin result in large decreases in renal sympathetic nerve activity and heart rate for a given increase in blood pressure as compared to progressive infusions of phenylephrine. In sinoaortic-denervated rabbits, the responses of arterial pressure on heart rate and renal sympathetic nerve activity to both arginine-vasopressin and phenylephrine are markedly attenuated, indicating the necessity for afferent baroreceptor activity in this response. This observation indicates that arginine-vasopressin is acting centrally to enhance the baroreflex. A central site of action of circulating vasopressin may be the area postrema, since it is the only circumventricular organ in the hindbrain. Lesioning the region of the area postrema resulted in a normalization of the responses evoked with arginine-vasopressin and phenylephrine. There was no difference in the phenylephrine responses of arterial pressure on renal sympathetic nerve activity or heart rate in area postrema-lesioned animals, compared to control rabbits. Therefore, we conclude that the area postrema or its surrounding tissue is either a site of action of circulating arginine-vasopressin or contains fibers of passage from another site where arginine-vasopressin acts to enhance baroreflex activity.

The present study was undertaken to determine whether gamma-aminobutyric acid in the paraventricular nucleus contributes to the regulation of cardiovascular function. Blood pressure and heart rate were recorded and plasma catecholamines were measured in conscious rats receiving microinfusions of either artificial cerebrospinal fluid or a gamma-aminobutyric acid antagonist, bicuculline methiodide, bilaterally into the paraventricular nucleus. Artificial cerebrospinal fluid had no effect on any of the recorded variables. In contrast, infusion of bicuculline into the region of the paraventricular nucleus produced increases in blood pressure (20 +/- 2 mm Hg), heart rate (110 +/- 11 beats/min), and plasma concentrations of norepinephrine (640 +/- 107 pg/ml) and epinephrine (1,266 +/- 267 pg/ml). Pretreatment with a ganglionic blocking agent abolished both the blood pressure (-1 +/- 2 mm Hg) and heart rate (5 +/- 18 beats/min) effects. Bilateral adrenal medullectomy reduced the changes in plasma norepinephrine concentrations (81 +/- 14 pg/ml) significantly and abolished the changes in plasma epinephrine concentrations (5 +/- 4 pg/ml). Conversely, adrenal medullectomy reduced the pressor effects (18 +/- 2 mm Hg) only slightly while the heart rate responses were attenuated (42 +/- 9 beats/min) by approximately 50%. These results suggest that an endogenous gamma-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus.