Contractions of amphibian Wolffian duct in response to acetylcholine, norepinephrine, and arginine vasotocin.

The regulation of sperm transport through the Wolffian duct of male amphibians is poorly understood. These experiments were conducted using rough-skinned newts (Taricha granulosa) to determine if Wolffian ducts are capable of contracting in vitro and, if so, to characterize the contractile responses to acetylcholine (ACh), norepinephrine (NE), and neurohypophysial hormones. Dose-response curves for NE and ACh, which were prepared by measuring isometric contractions, are similar to those reported for mammalian vas deferens. For NE, the minimum effective dose and ED50 were found to be 1 X 10(-5)M and 4.17 X 10(-5)M, respectively. For ACh, the minimum effective dose was 3.2 X 10(-8)M and the ED50 was 1.37 X 10(-5)M. Alpha-adrenoreceptors appear to mediate the contractile responses to NE because phentolamine (10(-5)M) blocked or attenuated the response to NE (10(-6)M, 10(-5)M or 10(-4) M). Beta-adrenoreceptors appear to mediate relaxation because dichloroisoproterenol (10(-5)M) enhanced the response to 10(-5)M NE. The contractile response to three neurohypophysial hormones were also investigated. Arginine vasotocin was more effective in eliciting contractions than oxytocin. The effect of lysine vasopressin was intermediate between arginine vasotocin and oxytocin. These experiments demonstrate that amphibian (Taricha) Wolffian ducts contract in vitro in response to neurotransmitters and neurohypophysial hormones. The contractile response to neurotransmitters occurs in a dose-dependent manner; the response to neurohypophysial hormones is hormone specific.

The effect of cold stress on the modulation of vascular adrenergic transmission by acetylcholine.

Acetylcholine acts via presynaptic receptors to inhibit adrenergic neurotransmission in vascular tissue. To test the possibility that this modulation might be altered by hyperactivity of the sympathetic nervous system, rats were exposed to cold stress for 5 days. Rat caudal (tail) arteries were excised, cannulated and perfused at constant flow. Responses to transmural nerve stimulation and/or acetylcholine were measured. In arteries from nonstressed rats, acetylcholine produced a dose-dependent inhibition of responses to nerve stimulation of 10 Hz. Likewise, acetylcholine (32 ng/ml) produced a frequency-dependent inhibition to nerve stimulation. Cold stress elevated sympathetic nerve activity in the tail artery as indicated by increased tyrosine hydroxylase activity. Responses to exogenous norepinephrine alone were not different between arteries from cold-stressed and nonstressed rats. In arteries from cold-stressed rats, acetylcholine inhibited the response to nerve stimulation in a dose-dependent manner and at each dose of acetylcholine the inhibition was greater than in arteries from nonstressed rats. Likewise, the inhibition of the frequency-dependent responses to nerve stimulation by acetylcholine was greater in arteries from cold-stressed than from nonstressed rats. These data show that after chronic elevation of vasomotor tone, acetylcholine is a more effective modulator of neurogenic tone which indicates the development of the functional equivalent of supersensitivity of presynaptic receptor-mediated events.

An 8 month longitudinal study of changes in elastic and muscular arteries and veins of the rabbit with sustained hypertension after abdominal aorta constriction.

1. Long-term changes in the function and structure of arteries and veins in response to an elevation in arterial pressure have been studied in the rabbit after partial abdominal aorta constriction. 2. Transient changes occur in the vasculature in association with the rise in arterial pressure. 3. The dominant change seen after arterial pressure elevation has been maintained for 8 months is an increase in arterial wall mass, including an increase in vascular smooth muscle cell number, and in some arteries an increase in internal diameter. 4. It may be inferred from this limited study of elastic and muscular arteries that structural alteration represents the over-riding response of the vasculature to an elevation in intramural pressure.

Vasoconstrictor hyperresponsiveness: an early pathogenic mechanism in the spontaneously hypertensive rat.

Factors which play a primary role in the initiation and development of hypertension in spontaneously hypertensive rats (SHR) are incompletely defined. To test the possibility that early changes in vascular function play a primary etiologic role, hindquarters of 3-week-old SHR and Wistar-Kyoto normotensive rats (WKY) were perfused at constant flow with plasma substitute. The vasculature of SHR exhibited higher resistance to flow than that of WKY. The threshold constrictor response to norepinephrine (NE) was elicited at a significantly lower concentration (6X) than required in WKY, while threshold to BaCl2 was not different. At concentrations of BaCl2 above threshold, SHR exhibited marked hyperresponsiveness compared to WKY. This resulted in a greater maximum response and thus a steeper slope. The ED50 for BaCl2 was not different. A similar dose--response relationship (greater maximum, steeper slope) was observed with NE except that the ED50 as well as threshold was significantly lower in SHR than in WKY. These data show that vasoconstrictor hyperresponsiveness and increased vascular resistance are present at the time when the hypertension is first detectable. The hyperresponsiveness includes two distinct components: (1) A specific hypersensitivity to NE and (2) non-specific hyperresponsiveness which could derive from altered excitation--contraction coupling and/or from a structural mechanism already present when pressure differences begin to appear.

Arterial pressure development in neonatal and young spontaneously hypertensive rats.

Systemic arterial pressure of spontaneously hypertensive rats (SHR) were not detectably different from control rats prior to 3 weeks of age. Arterial pressure was elevated in SHR at 4 weeks compared to Wistar-Kyoto rats. Thus, the term 'prehypertensive stage' should probably be reserved for animals less than 1 month of age when this model is examined.

Mechanism of vascular hyperresponsiveness in the spontaneously hypertensive rat.

Hyperresponsiveness of resistance vessels has been described in various vascular beds of spontaneously hypertensive rats perfused with artificial medium. This change has been attributed to altered vascular dimensions secondary to the development of hypertension. To test the possibility that true changes in sensitivity might contribute independently to vasoconstrictor hyperresponsiveness in spontaneously hypertensive rats, threshold vasoconstrictor doses of norepinephrine and barium chloride were determined in denervated hindquarters of rats perfused at constant flow with autologous blood. Threshold constrictor responses to norepinephrine were elicited in the hypertensive rats at concentrations averaging less than one-third that required in controls. Threshold vasoconstrictor concentrations of barium were not significantly different between the two groups. The ratio of norepinephrine/barium sensitivity was also significantly elevated in the hypertensive group. These data suggest that in the presence of a full humoral complement, excitability (barium sensitivity) in resistance vessels of spontaneously hypertensive rats is not altered, whereas the smooth muscle is hypersensitive to norepinephrine. Thus, it appears that changes in sensitivity as well as altered vascular geometry are important in the production of vascular hyperresponsiveness in the spontaneously hypertensive rat.