Contractile responses to electrical field stimulation of excised small mesenteric arteries and veins of the rat were compared when stimuli were delivered in irregular bursts or at regular intervals. Spontaneously occurring skin vasoconstrictor impulses in a few-unit median nerve recording in man were stored on tape and used to trigger a stimulator. Two irregular stimulation sequences at average frequencies of 1.6 and 1.8 Hz, respectively, were used. In the arteries, average contractile responses were significantly greater at an irregular than at an even stimulation frequency, but in the veins, similar degrees of contraction were obtained with the two modes of stimulation. The frequency-response relationships to continuous regular stimulation showed the artery to respond less than the vein at low frequencies. This apparently explains the differences in behaviour between the vessels to irregular stimulation. The results show that not only the number of impulses, but also their pattern of occurrence, may influence the degree of vasoconstriction. Thus, the normal irregular sympathetic discharge pattern in itself has a bearing on the physiology of neuro-effector control mechanisms.

The effects of distension on the sensitivity to noradrenaline and potassium were assessed in ring preparations of 200 micron branches from the superior mesenteric artery of the rat. In response to noradrenaline, maximal tension development occurred at smaller luminal diameters than with potassium activation. The sensitivity to noradrenaline increased with increasing distension whereas potassium sensitivity remained largely unchanged. A distension-dependent increase in noradrenaline sensitivity was observed also in vessels depolarized with high-potassium solution. The role of the distension-dependent sensitivity to noradrenaline for isotonic contractions was also studied. Upon activation with applied noradrenaline, submaximal isotonic responses were somewhat smaller than isometric responses at the same dose. This may be ascribed to a reduction in sensitivity during the isotonic contraction. Upon neurogenic activation, no difference between isotonic and isometric responses was found. The results show that distension increases noradrenaline sensitivity in resistance vessels in vitro, but that the consequences for their function as neuroeffectors may be small.

The role of the prejunctional alpha 2-receptors for the response to vaso-constrictor nerve stimulation has been examined before and after inhibition of neuronal transmitter reuptake in mesenteric resistance vessels from the rat. Small arteries (diameter about 200 micron) feeding the jejunum were mounted in a myograph for recording of their isometric wall tension during transmural field stimulation of the intramural nerves. Blockade of prejunctional alpha 2-receptors with 0.01 microM idazoxan (RX 781094) caused a marginal potentiation of the neurogenic response when neuronal reuptake was left intact. Also, inhibition of reuptake alone with 3 microM cocaine had little effect on the response. However, when both alpha 2-receptors and reuptake had been inhibited, a strong enhancement of the neurogenic vasoconstriction was observed. Similar findings were made when yohimbine and LU 3-010 instead were used for alpha 2-blockade and reuptake inhibition, respectively. The results thus indicate that in these resistance arteries the effector response is normally influenced by the combined activity of alpha 2-receptors and uptake, and that failure of one mechanism increases the activity of the other, so as to maintain a largely constant effector response.

Five current lines of cardiovascular studies in rats are outlined, mainly dealing with some functional and structural relationships of particular relevance for hypertension and ordinary aging: 1. Characteristics of the smooth muscles and their neurogenic control in 'Windkessel' arteries, conduit arteries, precapillary resistance vessels and venous capacitance vessels from normotensive rats (WKY) with comparisons to rats with primary hypertension (SHR). 2. Different types of structural renovascular adaptation, comparing aging with advancing SHR hypertension, with 'high-pressure' and 'low-pressure' kidneys in one-clip, two-kidney renal hypertension, and with hypertrophied kidneys in uni-nephrectomized normotensive rats. 3. Relationships between 'structural autoregulation', wall distensibility, vascular reactivity and smooth muscle sensitivity in SHR and WKY hindquarter resistance vessels along with aging. 4. Relationships between wall thickness, luminal dimension and contractility in left ventricles from SHR and WKY during aging, and when one-clip, two-kidney hypertension is superimposed. 5. Interference with the capacity of the neurohormonal mechanisms counteracting blood loss in rats when on chronic low-salt diet.

We have previously shown that, at least at frequencies of 4 Hz and above, a previous stimulation of the intramural vasoconstrictor nerves facilitates the subsequent response so that even maximal contractions can develop during periods of stimulation as short as a few seconds. In the present study the facilitating effect of a continuous nerve stimulation was quantitatively tested on 'single-twitch' responses to individual nerve impulses. Small arteries and veins (150-500 micron diameter) from rats were mounted in a myograph at known wall tension, and the intramural nerves were activated at frequencies between 0.1 and 32 Hz. After a period of continuous stimulation the single-twitch responses could be amplified 10-20 times, depending on frequency and duration of the continuous stimulation. No such amplification was observed after application of exogenous noradrenaline. The results therefore reflect a prejunctional frequency-dependent potentiating mechanism which can strongly reinforce sympathetic neuroeffector control. Furthermore, combined with previous data concerning adrenergic transmitter release, the present results seem to be more compatible with the view that the quantum of transmitter released from each varicosity upon activation is less than an entire granule.