Validation of the reference sample method (RSM) in the rat was accomplished by: 1) simultaneous measurement of cardiac output (CO) by the RSM and electromagnetic flowmetry method in ether-anesthetized open-chest Wistar rats, and 2) determination of systemic and regional hemodynamic reproducibility in conscious rats following three serial injections of microspheres. The optimal sampling time and sampling rate were determined in several CO states. The results indicate that: 1) 200 or more microspheres contained in the reference sample result in an accurate determination of CO, 2) almost 100% of the microspheres are trapped by tissues with in 20 s of cessation of the microsphere injection, 3) the hemodynamic steady state is affected only under low cardiac output conditions at a high sampling rate (1.211 ml/min), 4) three repeated injections of microspheres in conscious animals do not alter systemic hemodynamis, and 5) the reproducibility of regional blood flow distribution is good in all organs except the liver, stomach, spleen, and skin (third application). These data indicate that the RSM is reliable, providing reasonable accuracy and reproducibility of systemic and regional hemodynamics in the rat.

To study the effects of sodium intake on circulatory homeostasis and cardiac structure, changes in cardiac mass, systemic hemodynamics, and organ blood flows were determined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats after 10 wk of controlled dietary intake of low sodium (0.01%), standard sodium (0.44%), and high sodium (2 levels: 1.44 and 4%). Systemic and regional hemodynamics were measured in conscious rats using the radioactive microsphere reference method. The various dietary sodium manipulations did not cause any changes in systemic and regional hemodynamics in the WKY rats. In contrast, the high-sodium diets increased arterial pressure and total peripheral resistance progressively in the SHR rats while decreasing cardiac index, heart rate, and organ blood flows to heart, kidneys, and splanchnic area. The higher sodium intake (4%) increased total and left ventricular mass index in both the SHR and the WKY rats even though hemodynamics of the WKY rats remained unchanged. These data indicate that the high-sodium diet, in addition to producing general vasoconstriction and exacerbation of hypertension, increased cardiac mass further in SHR rats; it also increased cardiac mass in the WKY rats independent of arterial pressure changes, suggesting that high sodium intake may be an independent pathogenetic factor for the development of cardiac hypertrophy.

SUMMARY A segment of the facial vein of tbe rabbit, that opposite the buccal cavity, responds to norepinephrine (NE) and transmural nerve stimulation (TNS) by a brisk biphasic dilation. Tbe dilation in response to both procedures is reversed by prior exposure to propranolol (10"* M). Pretreatment with phenoxybenzamine (10" 6 M) increases the sire of the neurogenic response and displaces the NE dose-relaxation curve to tbe left. Histamine causes a constrictor response exclusively. Sympathetic stimulation of a segment of the facial vein proximal to this buccal segment, and also of tbe external jugular vein, results in constriction. light microscopy showed no features which can account for the dilation, and fluorescence histochemistry using a modified Fakk technique showed a dense adrenergk nerve plexus extending throughout the thickness of the media. We found that frequencyresponse characteristics and neuronal uptake of *H-NE were consistent with find in g« for a Mood vessel with a heavy medial innervation. Abo, monoamlne oxidase and catechol 0-methyltransfers** activities were similar to those found in other rabbit veins. Furthermore, these results are consistent with an adrenergk nearoeffector organization in which there is a predominance of /3-over a-adrenergic receptors. In conclusion, the presence of a dilator response in this buccal segment of the facial vein may be related to Its location in the wall of the cheek, where H may be subjected to considerable stretch.THE PRESENCE of both a-and /3-adrenergic receptors in vascular smooth muscle is undisputed.1 In most vascular preparations, however, the /3 effect of norepinephrine (NE) and neuronal activity is seen only after a-adrenergic receptor blockade. In other vessels the vasoconstriction induced by NE is increased after /3-receptor blockade.1 Autoregulatory escape can also be inhibited partially by /3-adrenergic receptor blocking agents.3 Although venous dilation can be brought about through /3-adrenergic receptor activation, 1 most isolated venous preparations contract in response to NE (e.g., see Bevan et al. 4 ). During the course of a survey of the adrenergic parameters of a number of rabbit veins, it was noted that, in contrast to all other veins studied, part of the facial vein responded to adrenergic stimuli with a biphasic relaxation. On a morphological study no features were found that would distinguish this part of the vein from portions on either side which contracted in response to stimulation. This study is concerned with the adrenergic properties of the relaxing part of this vein -the buccal segment of the anterior facial vein of the rabbit. MethodsAfter exsanguination of albino rabbits, segments of the external jugular and the facial veins were removed and placed in Krebs' bicarbonate solution gassed with 95 % O 2 and 5% CO 2 . The segments of the facial vein used in this study lie subcutaneously on the outside of the wall of the cheek. The vein is dissected from the lower border of the mandible to the confluence of the small veins that dra...

Prolonged treatment of spontaneously hypertensive (SHR) rats with either methyldopa or clonidine significantly and similarly reduced mean arterial pressure. Heart rate increased with methyldopa but decreased with clonidine; other haemodynamic effects were similar. SHR treated methyldopa, but not clonidine, had significantly reduced cardiac masses and heart weight to body weight ratios than did rats receiving the vehicle. Normotensive Wistar Kyoto (WKY) rats treated with methyldopa also had lower cardiac masses than their controls, but exhibited no significant changes in systemic haemodynamics. Treatment with the vasodilator hydralazine increased cardiac output and decreased total peripheral resistance in both SHR and WKY, but the decrease in mean arterial pressure was significant only in SHR. Heart rate was decreased and heart weight to body weight in WKY was elevated. Cardiac mass did not change. Minimal changes in regional haemodynamics were noted, with hydralazine eliciting a decrease in most organ vascular resistances. The data indicate that regression of hypertrophy following antihypertensive therapy was not solely dependent upon haemodynamic factors; nor was it necessarily the effect of suppression of the adrenergic system, since the results obtained with methyldopa and clonidine was similar.

Systemic and regional hemodynamic effects of intravenously injected calcitonin gene-related peptide (CGRP), 220 and 650 pmol, were compared in nine Wistar-Kyoto (WKY) and nine spontaneously hypertensive rats (SHR). CGRP (higher dose) reduced mean arterial pressure (from 135 +/- 2 to 83 +/- 2 and from 179 +/- 4 to 116 +/- 3 mmHg; P less than 0.01, each, in WKY and SHR, respectively) through a fall (-38 +/- 4 and -40 +/- 3%; P less than 0.01) in total peripheral resistance associated with an unchanged cardiac output and an increased heart rate. The decreases in arterial pressure and total peripheral resistance were not different between these two strains. Of particular significance were the highly selective reductions in organ vascular resistances, being greatest in the cutaneous (-78 +/- 3 and -67 +/- 4%) and gastric (-80 +/- 3 and -84 +/- 2%) circulations in WKY and SHR, respectively (P less than 0.01). Reduction in coronary, cerebral, and hepatic vascular resistances, although significant (P less than 0.05, at least), were only moderately reduced compared with the two former circulations. These effects were similar in WKY and SHR and demonstrate that CGRP is a highly selective and potent natural vasodilating peptide that has the most striking effects in skin and stomach, suggesting possible modulator functions in regulating certain regional hemodynamics.